Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto

ABSTRACT

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”).

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of, and claims the benefit of, U.S.nonprovisional application Ser. No. 16/203,690, which was filed Nov. 29,2018, now allowed; Ser. No. 16/203,690, is a continuation ofnonprovisional application Ser. No. 15/679,415, which was filed Aug. 17,2017, and is now U.S. Pat. No. 10,219,516; Ser. No. 15/679,415 is adivisional of, and claims the benefit of, U.S. nonprovisionalapplication Ser. No. 15/092,650, which was filed Apr. 7, 2016, and isnow U.S. Pat. No. 9,781,935; Ser. No. 15/092,650 claims the benefit of,and priority from, U.S. provisional application Ser. No. 62/148,809;62/148,814; 62/148,818; 62/148,824; 62/148,830; and 62/148,837; all ofwhich were filed on Apr. 17, 2015. The entire contents of all of theabove-identified applications are hereby incorporated by reference intothis application.

FIELD OF THIS DISCLOSURE

This disclosure relates to the field of molecules having pesticidalutility against pests in Phyla Arthropoda, Mollusca, and Nematoda,processes to produce such molecules, intermediates used in suchprocesses, pesticidal compositions containing such molecules, andprocesses of using such pesticidal compositions against such pests.These pesticidal compositions may be used, for example, as acaricides,insecticides, miticides, molluscicides, and nematicides.

BACKGROUND OF THIS DISCLOSURE

“Many of the most dangerous human diseases are transmitted by insectvectors” (Rivero et al.). “Historically, malaria, dengue, yellow fever,plague, filariasis, louse-borne typhus, trypanomiasis, leishmaniasis,and other vector borne diseases were responsible for more human diseaseand death in the 17^(th) through the early 20^(th) centuries than allother causes combined” (Gubler). Vector-borne diseases are responsiblefor about 17% of the global parasitic and infectious diseases. Malariaalone causes over 800,000 deaths a year, 85% of which occur in childrenunder five years of age. Each year there are about 50 to about 100million cases of dengue fever. A further 250,000 to 500,000 cases ofdengue hemorrhagic fever occur each year (Matthews). Vector controlplays a critical role in the prevention and control of infectiousdiseases. However, insecticide resistance, including resistance tomultiple insecticides, has arisen in all insect species that are majorvectors of human diseases (Rivero et al.). Recently, more than 550arthropod species have developed resistance to at least one pesticide(Whalon et al.). Furthermore, the cases of insect resistance continue toexceed by far the number of cases of herbicide and fungicide resistance(Sparks et al.).

Each year insects, plant pathogens, and weeds, destroy more than 40% ofall food production. This loss occurs despite the application ofpesticides and the use of a wide array of non-chemical controls, suchas, crop rotations, and biological controls. If just some of this foodcould be saved, it could be used to feed the more than three billionpeople in the world who are malnourished (Pimental).

Plant parasitic nematodes are among the most widespread pests, and arefrequently one of the most insidious and costly. It has been estimatedthat losses attributable to nematodes are from about 9% in developedcountries to about 15% in undeveloped countries. However, in the UnitedStates of America a survey of 35 States on various crops indicatednematode-derived losses of up to 25% (Nicol et al.).

It is noted that gastropods (slugs and snails) are pests of lesseconomic importance than other arthropods or nematodes, but in certainplaces, they may reduce yields substantially, severely affecting thequality of harvested products, as well as, transmitting human, animal,and plant diseases. While only a few dozen species of gastropods areserious regional pests, a handful of species are important pests on aworldwide scale. In particular, gastropods affect a wide variety ofagricultural and horticultural crops, such as, arable, pastoral, andfiber crops; vegetables; bush and tree fruits; herbs; and ornamentals(Speiser).

Termites cause damage to all types of private and public structures, aswell as to agricultural and forestry resources. In 2005, it wasestimated that termites cause over US$50 billion in damage worldwideeach year (Korb).

Consequently, for many reasons, including those mentioned above, thereis an on-going need for the costly (estimated to be about US$256 millionper pesticide in 2010), time-consuming (on average about 10 years perpesticide), and difficult, development of new pesticides (CropLifeAmerica).

CERTAIN REFERENCES CITED IN THIS DISCLOSURE

-   CropLife America, The Cost of New Agrochemical Product Discovery,    Development & Registration, and Research & Development predictions    for the Future, 2010.-   Drewes, M., Tietjen, K., Sparks, T. C., High-Throughput Screening in    Agrochemical Research, Modern Methods in Crop Protection Research,    Part I, Methods for the Design and Optimization of New Active    Ingredients, Edited by Jeschke, P., Kramer, W., Schirmer, U., and    Matthias W., p. 1-20, 2012.-   Gubler, D., Resurgent Vector-Borne Diseases as a Global Health    Problem, Emerging Infectious Diseases, Vol. 4, No. 3, p. 442-450,    1998.-   Korb, J., Termites, Current Biology, Vol. 17, No. 23, 2007.-   Matthews, G., Integrated Vector Management: Controlling Vectors of    Malaria and Other Insect Vector Borne Diseases, Ch. 1, p. 1, 2011.-   Nicol, J., Turner S., Coyne, L., den Nijs, L., Hocksland, L.,    Tahna-Maafi, Z., Current Nematode Threats to World Agriculture,    Genomic and Molecular Genetics of Plant—Nematode Interactions, p.    21-43, 2011.-   Pimental, D., Pest Control in World Agriculture, Agricultural    Sciences—Vol. II, 2009.-   Rivero, A., Vezilier, J., Weill, M., Read, A., Gandon, S., Insect    Control of Vector-Borne Diseases: When is Insect Resistance a    Problem? Public Library of Science Pathogens, Vol. 6, No. 8, p. 1-9,    2010.-   Sparks T. C., Nauen R., IRAC: Mode of action classification and    insecticide resistance management, Pesticide Biochemistry and    Physiology (2014) available online 4 Dec. 2014.-   Speiser, B., Molluscicides, Encyclopedia of Pest Management, Ch.    219, p. 506-508, 2002.-   Whalon, M., Mota-Sanchez, D., Hollingworth, R., Analysis of Global    Pesticide Resistance in Arthropods, Global Pesticide Resistance in    Arthropods, Ch. 1, p. 5-33, 2008.

DEFINITIONS USED IN THIS DISCLOSURE

The examples given in these definitions are generally non-exhaustive andmust not be construed as limiting this disclosure. It is understood thata substituent should comply with chemical bonding rules and stericcompatibility constraints in relation to the particular molecule towhich it is attached. These definitions are only to be used for thepurposes of this disclosure.

The phrase “active ingredient” means a material having activity usefulin controlling pests, and/or that is useful in helping other materialshave better activity in controlling pests, examples of such materialsinclude, but are not limited to, acaricides, algicides, antifeedants,avicides, bactericides, bird repellents, chemosterilants, fungicides,herbicide safeners, herbicides, insect attractants, insect repellents,insecticides, mammal repellents, mating disrupters, molluscicides,nematicides, plant activators, plant growth regulators, rodenticides,synergists, and virucides (see alanwood.net). Specific examples of suchmaterials include, but are not limited to, the materials listed inactive ingredient group alpha.

The phrase “active ingredient group alpha” (hereafter “AIGA”) meanscollectively the following materials:

(1) (3-ethoxypropyl)mercury bromide, 1,2-dibromoethane,1,2-dichloroethane, 1,2-dichloropropane, 1,3-dichloropropene, 1-MCP,1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,3-TPA,2,3,5-tri-iodobenzoic acid, 2,3,6-TBA, 2,4,5-T, 2,4,5-TB, 2,4,5-TP,2,4-D, 2,4-DB, 2,4-DEB, 2,4-DEP, 2,4-DES, 2,4-DP, 2,4-MCPA, 2,4-MCPB,2iP, 2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB,3,4-DP, 3,6-dichloropicolinic acid, 4-aminopyridine, 4-CPA, 4-CPB,4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate,8-phenylmercurioxyquinoline, abamectin, abamectin-aminomethyl, abscisicacid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor,acetofenate, acetophos, acetoprole, acibenzolar, acifluorfen, aclonifen,ACN, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs,afidopyropen, afoxolaner, alachlor, alanap, alanycarb, albendazole,aldicarb, aldicarb sulfone, aldimorph, aldoxycarb, aldrin, allethrin,allicin, allidochlor, allosamidin, alloxydim, allyl alcohol, allyxycarb,alorac, alpha-cypermethrin, alpha-endosulfan, alphamethrin, altretamine,aluminium phosphide, aluminum phosphide, ametoctradin, ametridione,ametryn, ametryne, amibuzin, amicarbazone, amicarthiazol, amidithion,amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor,aminopyralid, aminotriazole, amiprofos-methyl, amiprophos,amiprophos-methyl, amisulbrom, amiton, amitraz, amitrole, ammoniumsulfamate, amobam, amorphous silica gel, amorphous silicon dioxide,ampropylfos, AMS, anabasine, ancymidol, anilazine, anilofos, anisuron,anthraquinone, antu, apholate, aramite, arprocarb, arsenous oxide,asomate, aspirin, asulam, athidathion, atraton, atrazine, aureofungin,avermectin B1, AVG, aviglycine, azaconazole, azadirachtin, azafenidin,azamethiphos, azidithion, azimsulfuron, azinphosethyl, azinphos-ethyl,azinphosmethyl, azinphos-methyl, aziprotryn, aziprotryne, azithiram,azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban,barbanate, barium hexafluorosilicate, barium polysulfide, bariumsilicofluoride, barthrin, basic copper carbonate, basic copper chloride,basic copper sulfate, BCPC, beflubutamid, benalaxyl, benalaxyl-M,benazolin, bencarbazone, benclothiaz, bendaqingbingzhi, bendiocarb,bendioxide, benefin, benfluralin, benfuracarb, benfuresate,benmihuangcaoan, benodanil, benomyl, benoxacor, benoxafos, benquinox,bensulfuron, bensulide, bensultap, bentaluron, bentazon, bentazone,benthiavalicarb, benthiazole, benthiocarb, bentranil, benzadox,benzalkonium chloride, benzamacril, benzamizole, benzamorf, benzenehexachloride, benzfendizone, benzimine, benzipram, benzobicyclon,benzoepin, benzofenap, benzofluor, benzohydroxamic acid, benzomate,benzophosphate, benzothiadiazole, benzovindiflupyr, benzoximate,benzoylprop, benzthiazuron, benzuocaotong, benzyl benzoate,benzyladenine, berberine, beta-cyfluthrin, beta-cypermethrin,bethoxazin, BHC, bialaphos, bicyclopyrone, bifenazate, bifenox,bifenthrin, bifujunzhi, bilanafos, binapacryl, bingqingxiao,bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl,bisazir, bismerthiazol, bismerthiazol-copper, bisphenylmercurymethylenedi(x-naphthalene-y-sulphonate), bispyribac, bistrifluron,bisultap, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeauxmixture, boric acid, boscalid, BPPS, brassinolide, brassinolide-ethyl,brevicomin, brodifacoum, brofenprox, brofenvalerate, broflanilide,brofluthrinate, bromacil, bromadiolone, bromchlophos, bromethalin,bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide,bromociclen, bromocyclen, bromo-DDT, bromofenoxim, bromofos,bromomethane, bromophos, bromophos-ethyl, bromopropylate, bromothalonil,bromoxynil, brompyrazon, bromuconazole, bronopol, BRP, BTH, bucarpolate,bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture,busulfan, busulphan, butacarb, butachlor, butafenacil, butam, butamifos,butane-fipronil, butathiofos, butenachlor, butene-fipronil, butethrin,buthidazole, buthiobate, buthiuron, butifos, butocarboxim, butonate,butopyronoxyl, butoxycarboxim, butralin, butrizol, butroxydim, buturon,butylamine, butylate, butylchlorophos, butylene-fipronil, cacodylicacid, cadusafos, cafenstrole, calciferol, calcium arsenate, calciumchlorate, calcium cyanamide, calcium cyanide, calcium polysulfide,calvinphos, cambendichlor, camphechlor, camphor, captafol, captan,carbam, carbamorph, carbanolate, carbaril, carbaryl, carbasulam,carbathion, carbendazim, carbendazol, carbetamide, carbofenotion,carbofuran, carbon disulfide, carbon tetrachloride, carbonyl sulfide,carbophenothion, carbophos, carbosulfan, carboxazole, carboxide,carboxin, carfentrazone, carpropamid, cartap, carvacrol, carvone, CAVP,CDAA, CDEA, CDEC, cellocidin, CEPC, ceralure, cerenox, cevadilla,Cheshunt mixture, chinalphos, chinalphos-methyl, chinomethionat,chinomethionate, chiralaxyl, chitosan, chlobenthiazone, chlomethoxyfen,chloralose, chloramben, chloramine phosphorus, chloramphenicol,chloraniformethan, chloranil, chloranocryl, chlorantraniliprole,chlorazifop, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen,chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform,chlorempenthrin, chloretazate, chlorethephon, chlorethoxyfos,chloreturon, chlorfenac, chlorfenapyr, chlorfenazole, chlorfenethol,chlorfenidim, chlorfenprop, chlorfenson, chlorfensulphide,chlorfenvinphos, chlorfenvinphos-methyl, chlorfluazuron, chlorflurazole,chlorflurecol, chlorfluren, chlorflurenol, chloridazon, chlorimuron,chlorinate, chlor-IPC, chlormephos, chlormequat, chlormesulone,chlormethoxynil, chlornidine, chlornitrofen, chloroacetic acid,chlorobenzilate, chlorodinitronaphthalenes, chlorofenizon, chloroform,chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophos,chloropicrin, chloropon, chloropropylate, chlorothalonil, chlorotoluron,chloroxifenidim, chloroxuron, chloroxynil, chlorphonium, chlorphoxim,chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos,chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal,chlorthiamid, chlorthiophos, chlortoluron, chlozolinate, chltosan,cholecalciferol, choline chloride, chromafenozide, cicloheximide,cimectacarb, cimetacarb, cinerin I, cinerin II, cinerins, cinidon-ethyl,cinmethylin, cinosulfuron, cintofen, ciobutide, cisanilide, cismethrin,clacyfos, clefoxydim, clenpirin, clenpyrin, clethodim, climbazole,cliodinate, clodinafop, cloethocarb, clofencet, clofenotane,clofentezine, clofenvinfos, clofibric acid, clofop, clomazone,clomeprop, clonitralid, cloprop, cloproxydim, clopyralid, cloquintocet,cloransulam, closantel, clothianidin, clotrimazole, cloxyfonac,cloxylacon, clozylacon, CMA, CMMP, CMP, CMU, codlelure, colecalciferol,colophonate, copper 8-quinolinolate, copper acetate, copperacetoarsenite, copper arsenate, copper carbonate, basic, copperhydroxide, copper naphthenate, copper oleate, copper oxychloride, coppersilicate, copper sulfate, copper sulfate, basic, copper zinc chromate,coumachlor, coumafène, coumafos, coumafuryl, coumaphos, coumatetralyl,coumethoxystrobin, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC,credazine, cresol, cresylic acid, crimidine, crotamiton, crotoxyfos,crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyleron,cumyluron, cuprobam, cuprous oxide, curcumenol, CVMP, cyanamide,cyanatryn, cyanazine, cyanofenphos, cyanogen, cyanophos, cyanthoate,cyantraniliprole, cyanuric acid, cyazofamid, cybutryne, cyclafuramid,cyclanilide, cyclaniliprole, cyclethrin, cycloate, cycloheximide,cycloprate, cycloprothrin, cyclopyrimorate, cyclosulfamuron, cycloxydim,cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin,cyhalofop, cyhalothrin, cyhexatin, cymiazole, cymoxanil, cyometrinil,cypendazole, cypermethrin, cyperquat, cyphenothrin, cyprazine,cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid,cyprosulfamide, cyromazine, cythioate, cytrex, daimuron, dalapon,daminozide, dayoutong, dazomet, DBCP, d-camphor, DCB, DCIP, DCPA, DCPTA,DCU, DDD, DDPP, DDT, DDVP, debacarb, decafentin, decamethrin,decarbofuran, deet, dehydroacetic acid, deiquat, delachlor, delnav,deltamethrin, demephion, demephion-O, demephion-S, demeton,demeton-methyl, demeton-O, demeton-O-methyl, demeton-S,demeton-S-methyl, demeton-S-methyl sulphone, demeton-S-methylsulphon,DEP, depalléthrine, derris, desmedipham, desmetryn, desmetryne,d-fanshiluquebingjuzhi, diafenthiuron, dialifor, dialifos, diallate,diamidafos, dianat, diatomaceous earth, diatomite, diazinon, dibrom,dibutyl phthalate, dibutyl succinate, dicamba, dicapthon, dichlobenil,dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron,dichlorfenidim, dichlorflurecol, dichlorflurenol, dichlormate,dichlormid, dichloromethane, dicloromezotiaz, dichlorophen, dichlorprop,dichlorprop-P, dichlorvos, dichlozolin, dichlozoline, diclobutrazol,diclocymet, diclofop, diclomezine, dicloran, diclosulam, dicofol,dicophane, dicoumarol, dicresyl, dicrotophos, dicryl, dicumarol,dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethatyl,diethion, diethion, diethofencarb, dietholate, diethon, diethylpyrocarbonate, diethyltoluamide, difenacoum, difenoconazole,difenopenten, difenoxuron, difenzoquat, difethialone, diflovidazin,diflubenzuron, diflufenican, diflufenicanil, diflufenzopyr,diflumetorim, dikegulac, dilor, dimatif, dimefluthrin, dimefox,dimefuron, dimehypo, dimepiperate, dimetachlone, dimetan, dimethacarb,dimethachlone, dimethachlor, dimethametryn, dimethenamid,dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph,dimethrin, dimethyl carbate, dimethyl disulfide, dimethyl phthalate,dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin,dimpylate, dimuron, dinex, dingjunezuo, diniconazole, diniconazole-M,dinitramine, dinitrophenols, dinobuton, dinocap, dinocap-4, dinocap-6,dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb,dinosulfon, dinotefuran, dinoterb, dinoterbon, diofenolan,dioxabenzofos, dioxacarb, dioxathion, dioxation, diphacin, diphacinone,diphenadione, diphenamid, diphenamide, diphenyl sulfone, diphenylamine,diphenylsulphide, diprogulic acid, dipropalin, dipropetryn, dipterex,dipymetitrone, dipyrithione, diquat, disodium tetraborate, disosultap,disparlure, disugran, disul, disulfiram, disulfoton, ditalimfos,dithianon, dithicrofos, dithioether, dithiometon, dithiopyr, diuron,dixanthogen, d-limonene, DMDS, DMPA, DNOC, dodemorph, dodicin, dodine,dofenapyn, doguadine, dominicalure, doramectin, DPC, drazoxolon, DSMA,d-trans-allethrin, d-trans-resmethrin, dufulin, dymron, EBEP, EBP,ebufos, ecdysterone, echlomezol, EDB, EDC, EDDP, edifenphos, eglinazine,emamectin, EMPC, empenthrin, enadenine, endosulfan, endothal, endothall,endothion, endrin, enestroburin, enilconazole, enoxastrobin,ephirsulfonate, EPN, epocholeone, epofenonane, epoxiconazole,eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan,esdepallthrine, esfenvalerate, ESP, esprocarb, etacelasil, etaconazole,etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron,ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion,ethiozin, ethiprole, ethirimol, ethoate-methyl, ethobenzanid,ethofumesate, ethohexadiol, ethoprop, ethoprophos, ethoxyfen,ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethylpyrophosphate, ethylan, ethyl-DDD, ethylene, ethylene dibromide,ethylene dichloride, ethylene oxide, ethylicin, ethylmercury2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercurybromide, ethylmercury chloride, ethylmercury phosphate, etinofen, ETM,etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos,etrimphos, eugenol, EXD, famoxadone, famphur, fenac, fenamidone,fenaminosulf, fenaminstrobin, fenamiphos, fenapanil, fenarimol,fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide,fenchlorazole, fenchlorphos, fenclofos, fenclorim, fenethacarb,fenfluthrin, fenfuram, fenhexamid, fenidin, fenitropan, fenitrothion,fenizon, fenjuntong, fenobucarb, fenolovo, fenoprop, fenothiocarb,fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-P, fenoxasulfone,fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin,fenpropimorph, fenpyrazamine, fenpyroximate, fenquinotrione, fenridazon,fenson, fensulfothion, fenteracol, fenthiaprop, fenthion,fenthion-ethyl, fentiaprop, fentin, fentrazamide, fentrifanil, fenuron,fenuron-TCA, fenvalerate, ferbam, ferimzone, ferric phosphate, ferroussulfate, fipronil, flamprop, flamprop-M, flazasulfuron, flocoumafen,flometoquin, flonicamid, florasulam, fluacrypyrim, fluazifop,fluazifop-P, fluazinam, fluazolate, fluazuron, flubendiamide,flubenzimine, flubrocythrinate, flucarbazone, flucetosulfuron,fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil,fluénéthyl, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican,flufenoxuron, flufenoxystrobin, flufenprox, flufenpyr, flufenzine,flufiprole, fluhexafon, flumethrin, flumetover, flumetralin,flumetsulam, flumezin, flumiclorac, flumioxazin, flumipropyn, flumorph,fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid,fluoroacetamide, fluoroacetic acid, fluorochloridone, fluorodifen,fluoroglycofen, fluoroimide, fluoromide, fluoromidine, fluoronitrofen,fluoroxypyr, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam,flupropacil, flupropadine, flupropanate, flupyradifurone,flupyrsulfuron, fluquinconazole, fluralaner, flurazole, flurecol,flurenol, fluridone, flurochloridone, fluromidine, fluroxypyr,flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide,flutenzine, fluthiacet, fluthiamide, flutianil, flutolanil, flutriafol,fluvalinate, fluxapyroxad, fluxofenim, folpel, folpet, fomesafen,fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate,formothion, formparanate, fosamine, fosetyl, fosmethilan, fospirate,fosthiazate, fosthietan, frontalin, fthalide, fuberidazole, fucaojing,fucaomi, fujunmanzhi, fulumi, fumarin, funaihecaoling, fuphenthiourea,furalane, furalaxyl, furamethrin, furametpyr, furan tebufenozide,furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin,furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-BHC,gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellin A3,gibberellins, gliftor, glitor, glucochloralose, glufosinate,glufosinate-P, glyodin, glyoxime, glyphosate, glyphosine, gossyplure,grandlure, griseofulvin, guanoctine, guazatine, halacrinate, halauxifen,halfenprox, halofenozide, halosafen, halosulfuron, haloxydine,haloxyfop, haloxyfop-P, haloxyfop-R, HCA, HCB, HCH, hemel, hempa, HEOD,heptachlor, heptafluthrin, heptenophos, heptopargil, herbimycin,herbimycin A, heterophos, hexachlor, hexachloran, hexachloroacetone,hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole,hexaflumuron, hexafluoramin, hexaflurate, hexalure, hexamide,hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, homobrassinolide,huancaiwo, huanchongjing, huangcaoling, huanjunzuo, hydramethylnon,hydrargaphen, hydrated lime, hydrogen cyanamide, hydrogen cyanide,hydroprene, hydroxyisoxazole, hymexazol, hyquincarb, IAA, IBA, IBP,icaridin, imazalil, imazamethabenz, imazamox, imazapic, imazapyr,imazaquin, imazethapyr, imazosulfuron, imibenconazole, imicyafos,imidacloprid, imidaclothiz, iminoctadine, imiprothrin, inabenfide,indanofan, indaziflam, indoxacarb, inezin, infusorial earth, iodobonil,iodocarb, iodofenphos, iodomethane, iodosulfuron, iofensulfuron,ioxynil, ipazine, IPC, ipconazole, ipfencarbazone, iprobenfos,iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, IPX,isamidofos, isazofos, isobenzan, isocarbamid, isocarbamide,isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl,isofetamid, isolan, isomethiozin, isonoruron, isopamphos, isopolinate,isoprocarb, isoprocil, isopropalin, isopropazol, isoprothiolane,isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron,isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxaflutole,isoxapyrifop, isoxathion, isuron, ivermectin, ixoxaben, izopamfos,izopamphos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonicacid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan,jiecaoxi, jinganmycin A, jodfenphos, juvenile hormone I, juvenilehormone II, juvenile hormone III, kadethrin, kappa-bifenthrin,kappa-tefluthrin, karbutilate, karetazan, kasugamycin, kejunlin,kelevan, ketospiradox, kieselguhr, kinetin, kinoprene, kiralaxyl,kresoxim-methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure, leadarsenate, lenacil, lepimectin, leptophos, lianbenjingzhi, lime sulfur,lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron,lüxiancaolin, lvdingjunzhi, lvfumijvzhi, lvxiancaolin, lythidathion,M-74, M-81, MAA, magnesium phosphide, malathion, maldison, maleichydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb,mandestrobin, mandipropamid, maneb, matrine, mazidox, MCC, MCP, MCPA,MCPA-thioethyl, MCPB, MCPP, mebenil, mecarbam, mecarbinzid, mecarphon,mecoprop, mecoprop-P, medimeform, medinoterb, medlure, mefenacet,mefenoxam, mefenpyr, mefluidide, megatomoic acid, melissyl alcohol,melitoxin, MEMC, menazon, MEP, mepanipyrim, meperfluthrin, mephenate,mephosfolan, mepiquat, mepronil, meptyldinocap, mercaptodimethur,mercaptophos, mercaptophos thiol, mercaptothion, mercuric chloride,mercuric oxide, mercurous chloride, merphos, merphos oxide, mesoprazine,mesosulfuron, mesotrione, mesulfen, mesulfenfos, mesulphen, metacresol,metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metamifop,metamitron, metaphos, metaxon, metazachlor, metazosulfuron, metazoxolon,metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos,methalpropalin, metham, methamidophos, methasulfocarb, methazole,methfuroxam, methibenzuron, methidathion, methiobencarb, methiocarb,methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos,métholcarb, methometon, methomyl, methoprene, methoprotryn,methoprotryne, methoquin-butyl, methothrin, methoxychlor,methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyleugenol, methyl iodide, methyl isothiocyanate, methyl parathion,methylacetophos, methylchloroform, methyldithiocarbamic acid,methyldymron, methylene chloride, methyl-isofenphos, methylmercaptophos,methylmercaptophos oxide, methylmercaptophos thiol, methylmercurybenzoate, methylmercury dicyandiamide, methylmercurypentachlorophenoxide, methylneodecanamide, methylnitrophos,methyltriazothion, metiozolin, metiram, metiram-zinc, metobenzuron,metobromuron, metofluthrin, metolachlor, metolcarb, metometuron,metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone,metriam, metribuzin, metrifonate, metriphonate, metsulfovax,metsulfuron, mevinphos, mexacarbate, miechuwei, mieshuan, miewenjuzhi,milbemectin, milbemycin oxime, milneb, mima2nan, mipafox, MIPC, mirex,MNAF, moguchun, molinate, molosultap, momfluorothrin, monalide,monisuron, monoamitraz, monochloroacetic acid, monocrotophos,monolinuron, monomehypo, monosulfiram, monosulfuron, monosultap,monuron, monuron-TCA, morfamquat, moroxydine, morphothion, morzid,moxidectin, MPMC, MSMA, MTMC, muscalure, myclobutanil, myclozolin,myricyl alcohol, N-(ethylmercury)-p-toluenesulphonanilide, NAA, NAAm,nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalicanhydride, naphthalophos, naphthoxyacetic acids, naphthylacetic acids,naphthylindane-1,3-diones, naphthyloxyacetic acids, naproanilide,napropamide, napropamide-M, naptalam, natamycin, NBPOS, neburea,neburon, nendrin, neonicotine, nichlorfos, niclofen, niclosamide,nicobifen, nicosulfuron, nicotine, nicotine sulfate, nifluridide,nikkomycins, NIP, nipyraclofen, nipyralofen, nitenpyram, nithiazine,nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen,nitrostyrene, nitrothal-isopropyl, nobormide, nonanol, norbormide,norea, norflurazon, nornicotine, noruron, novaluron, noviflumuron, NPA,nuarimol, nuranone, OCH, octachlorodipropyl ether, octhilinone,o-dichlorobenzene, ofurace, omethoate, o-phenylphenol, orbencarb,orfralure, orthobencarb, ortho-dichlorobenzene, orthosulfamuron,oryctalure, orysastrobin, oryzalin, osthol, osthole, ostramone, ovatron,ovex, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl,oxapyrazon, oxapyrazone, oxasulfuron, oxathiapiprolin, oxaziclomefone,oxine-copper, oxine-Cu, oxolinic acid, oxpoconazole, oxycarboxin,oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyenadenine,oxyfluorfen, oxymatrine, oxytetracycline, oxythioquinox, PAC,paclobutrazol, paichongding, pallthrine, PAP, para-dichlorobenzene,parafluron, paraquat, parathion, parathion-methyl, parinol, Paris green,PCNB, PCP, PCP-Na, p-dichlorobenzene, PDJ, pebulate, pédinex,pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin,penfenate, penflufen, penfluron, penoxalin, penoxsulam,pentachlorophenol, pentachlorophenyl laurate, pentanochlor,penthiopyrad, pentmethrin, pentoxazone, perchlordecone, perfluidone,permethrin, pethoxamid, PHC, phenamacril, phenamacril-ethyl,phénaminosulf, phenazine oxide, phenetacarbe, phenisopham, phenkapton,phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothiol, phenothrin,phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate,phenylmercury chloride, phenylmercury derivative of pyrocatechol,phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim,phosalone, phosametine, phosazetim, phosazetin, phoscyclotin,phosdiphen, phosethyl, phosfolan, phosfolan-methyl, phosglycin, phosmet,phosnichlor, phosphamide, phosphamidon, phosphine, phosphinothricin,phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide,phthalophos, phthalthrin, picarbutrazox, picaridin, picloram,picolinafen, picoxystrobin, pimaricin, pindone, pinoxaden, piperalin,piperazine, piperonyl butoxide, piperonyl cyclonene, piperophos,piproctanly, piproctanyl, piprotal, pirimetaphos, pirimicarb, piriminil,pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, pival, pivaldione,plifenate, PMA, PMP, polybutenes, polycarbamate, polychlorcamphene,polyethoxyquinoline, polyoxin D, polyoxins, polyoxorim, polythialan,potassium arsenite, potassium azide, potassium cyanate, potassiumethylxanthate, potassium naphthenate, potassium polysulfide, potassiumthiocyanate, pp′-DDT, prallethrin, precocene I, precocene II, precoceneIII, pretilachlor, primidophos, primisulfuron, probenazole, prochloraz,proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol,profluralin, profluthrin, profoxydim, profurite-aminium, proglinazine,prohexadione, prohydrojasmon, promacyl, promecarb, prometon, prometryn,prometryne, promurit, pronamide, propachlor, propafos, propamidine,propamocarb, propanil, propaphos, propaquizafop, propargite,proparthrin, propazine, propetamphos, propham, propiconazole, propidine,propineb, propisochlor, propoxur, propoxycarbazone, propyl isome,propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin,prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothioconazole,prothiofos, prothoate, protrifenbute, proxan, prymidophos, prynachlor,psoralen, psoralene, pydanon, pyflubumide, pymetrozine, pyracarbolid,pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyrafluprole,pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyraziflumid,pyrazolate, pyrazolynate, pyrazon, pyrazophos, pyrazosulfuron,pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II,pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb,pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl,pyridaphenthion, pyridaphenthione, pyridate, pyridinitril, pyrifenox,pyrifluquinazon, pyriftalid, pyrimetaphos, pyrimethanil, pyrimicarbe,pyrimidifen, pyriminobac, pyriminostrobin, pyrimiphos-ethyl,pyrimiphos-methyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone,pyriprole, pyripropanol, pyriproxyfen, pyrisoxazole, pyrithiobac,pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur,qincaosuan, qingkuling, quassia, quinacetol, quinalphos,quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac,quinoclamine, quinomethionate, quinonamid, quinothion, quinoxyfen,quintiofos, quintozene, quizalofop, quizalofop-P, quwenzhi, quyingding,rabenzazole, rafoxanide, R-diniconazole, rebemide, reglone, renriduron,rescalure, resmethrin, rhodethanil, rhodojaponin-III, ribavirin,rimsulfuron, rizazole, R-metalaxyl, rodethanil, ronnel, rotenone,ryania, sabadilla, saflufenacil, saijunmao, saisentong, salicylanilide,salifluofen, sanguinarine, santonin, S-bioallethrin, schradan,scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin,semiamitraz, sesamex, sesamolin, sesone, sethoxydim, sevin,shuangjiaancaolin, shuangjianancaolin, S-hydroprene, siduron,sifumijvzhi, siglure, silafluofen, silatrane, silica aerogel, silicagel, silthiofam, silthiopham, silthiophan, silvex, simazine,simeconazole, simeton, simetryn, simetryne, sintofen, S-kinoprene,slaked lime, SMA, S-methoprene, S-metolachlor, sodium arsenite, sodiumazide, sodium chlorate, sodium cyanide, sodium fluoride, sodiumfluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodiumo-phenylphenoxide, sodium orthophenylphenoxide, sodiumpentachlorophenate, sodium pentachlorophenoxide, sodium polysulfide,sodium silicofluoride, sodium tetrathiocarbonate, sodium thiocyanate,solan, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen,spirotetramat, spiroxamine, stirofos, streptomycin, strychnine,sulcatol, sulcofuron, sulcotrione, sulfallate, sulfentrazone, sulfiram,sulfluramid, sulfodiazole, sulfometuron, sulfosate, sulfosulfuron,sulfotep, sulfotepp, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuricacid, sulfuryl fluoride, sulglycapin, sulphosate, sulprofos, sultropen,swep, tau-fluvalinate, tavron, tazimcarb, TBTO, TBZ, TCA, TCBA, TCMTB,TCNB, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin,tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram,tedion, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temefos,temephos, tepa, TEPP, tepraloxydim, teproloxydim, terallethrin,terbacil, terbucarb, terbuchlor, terbufos, terbumeton, terbuthylazine,terbutol, terbutryn, terbutryne, terraclor, terramicin, terramycin,tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole,tetradifon, tetradisul, tetrafluron, tetramethrin, tetramethylfluthrin,tetramine, tetranactin, tetraniliprole, tetrapion, tetrasul, thalliumsulfate, thallous sulfate, thenylchlor, theta-cypermethrin,thiabendazole, thiacloprid, thiadiazine, thiadifluor, thiamethoxam,thiameturon, thiapronil, thiazafluron, thiazfluron, thiazone, thiazopyr,thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone,thifensulfuron, thifluzamide, thimerosal, thimet, thiobencarb,thiocarboxime, thiochlorfenphim, thiochlorphenphime,thiocyanatodinitrobenzenes, thiocyclam, thiodan, thiodiazole-copper,thiodicarb, thiofanocarb, thiofanox, thiofluoximate, thiohempa,thiomersal, thiometon, thionazin, thiophanate, thiophanate-ethyl,thiophanate-methyl, thiophos, thioquinox, thiosemicarbazide, thiosultap,thiotepa, thioxamyl, thiram, thiuram, thuringiensin, tiabendazole,tiadinil, tiafenacil, tiaojiean, TIBA, tifatol, tiocarbazil, tioclorim,tioxazafen, tioxymid, tirpate, TMTD, tolclofos-methyl, tolfenpyrad,tolprocarb, tolpyralate, tolyfluanid, tolylfluanid, tolylmercuryacetate, tomarin, topramezone, toxaphene, TPN, tralkoxydim,tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin,tretamine, triacontanol, triadimefon, triadimenol, triafamone,triallate, tri-allate, triamiphos, triapenthenol, triarathene,triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos,triazothion, triazoxide, tribasic copper chloride, tribasic coppersulfate, tribenuron, tribufos, tributyltin oxide, tricamba, trichlamide,trichlopyr, trichlorfon, trichlormetaphos-3, trichloronat,trichloronate, trichlorotrinitrobenzenes, trichlorphon, triclopyr,triclopyricarb, tricresol, tricyclazole, tricyclohexyltin hydroxide,tridemorph, tridiphane, trietazine, trifenmorph, trifenofos,trifloxystrobin, trifloxysulfuron, trifludimoxazin, triflumezopyrim,triflumizole, triflumuron, trifluralin, triflusulfuron, trifop,trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb,trimeturon, trinexapac, triphenyltin, triprene, tripropindan,triptolide, tritac, trithialan, triticonazole, tritosulfuron,trunc-call, tuoyelin, uniconazole, uniconazole-P, urbacide, uredepa,valerate, validamycin, validamycin A, valifenalate, valone, vamidothion,vangard, vaniliprole, vernolate, vinclozolin, vitamin D3, warfarin,xiaochongliulin, xinjunan, xiwojunan, xiwojunzhi, XMC, xylachlor,xylenols, xylylcarb, xymiazole, yishijing, zarilamid, zeatin,zengxiaoan, zengxiaolin, zeta-cypermethrin, zinc naphthenate, zincphosphide, zinc thiazole, zinc thiozole, zinc trichlorophenate, zinctrichlorophenoxide, zineb, ziram, zolaprofos, zoocoumarin, zoxamide,zuoanjunzhi, zuocaoan, zuojunzhi, zuomihuanglong, α-chlorohydrin,α-ecdysone, α-multistriatin, α-naphthaleneacetic acids, and β-ecdysone;

(2) the following molecules

-   -   (a)        N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide        (hereafter “AI-1”)

-   -   (b)        (3S,6S,7R,8R)-8-benzyl-3-(3-((isobutyryloxy)methoxy)-4-methoxypicolinamido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl        isobutyrate (hereafter “AI-2”)

(3) a molecule known as Lotilaner that has the following structure

(4) the following molecules in Table A

TABLE A Structure of M# - active ingredients M# Structure M1

M2

M3

M4

M5

M6

As used in this disclosure, each of the above is an active ingredient.For more information consult the “Compendium of Pesticide Common Names”located at Alanwood.net and various editions, including the on-lineedition, of “The Pesticide Manual” located at bcpcdata.com.

A particularly preferred selection of active ingredients are 1,3dichloropropene, chlorpyrifos, hexaflumuron, methoxyfenozide,noviflumuron, spinetoram, spinosad, and sulfoxaflor (hereafter“AIGA-2”).

Additionally, another particularly preferred selection of activeingredients are acequinocyl, acetamiprid, acetoprole, avermectin,azinphos-methyl, bifenazate, bifenthrin, carbaryl, carbofuran,chlorfenapyr, chlorfluazuron, chromafenozide, clothianidin, cyfluthrin,cypermethrin, deltamethrin, diafenthiuron, emamectin benzoate,endosulfan, esfenvalerate, ethiprole, etoxazole, fipronil, flonicamid,fluacrypyrim, gamma-cyhalothrin, halofenozide, indoxacarb,lambda-cyhalothrin, lufenuron, malathion, methomyl, novaluron,permethrin, pyridalyl, pyrimidifen, spirodiclofen, tebufenozide,thiacloprid, thiamethoxam, thiodicarb, tolfenpyrad, andzeta-cypermethrin (hereafter “AIGA-3”).

The term “alkenyl” means an acyclic, unsaturated (at least onecarbon-carbon double bond), branched or unbranched, substituentconsisting of carbon and hydrogen, for example, vinyl, allyl, butenyl,pentenyl, and hexenyl.

The term “alkenyloxy” means an alkenyl further consisting of acarbon-oxygen single bond, for example, allyloxy, butenyloxy,pentenyloxy, hexenyloxy.

The term “alkoxy” means an alkyl further consisting of a carbon-oxygensingle bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy,isobutoxy, and tertbutoxy.

The term “alkyl” means an acyclic, saturated, branched or unbranched,substituent consisting of carbon and hydrogen, for example, methyl,ethyl, propyl, isopropyl, butyl, and tertbutyl.

The term “alkynyl” means an acyclic, unsaturated (at least onecarbon-carbon triple bond), branched or unbranched, substituentconsisting of carbon and hydrogen, for example, ethynyl, propargyl,butynyl, and pentynyl.

The term “alkynyloxy” means an alkynyl further consisting of acarbon-oxygen single bond, for example, pentynyloxy, hexynyloxy,heptynyloxy, and octynyloxy.

The term “aryl” means a cyclic, aromatic substituent consisting ofhydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.

The term “biopesticide” means a microbial biological pest control agentthat, in general, is applied in a similar manner to chemical pesticides.Commonly they are bacterial, but there are also examples of fungalcontrol agents, including Trichoderma spp. and Ampelomyces quisqualis.One well-known biopesticide example is Bacillus species, a bacterialdisease of Lepidoptera, Coleoptera, and Diptera. Biopesticides includeproducts based on entomopathogenic fungi (e.g. Metarhizium anisopliae),entomopathogenic nematodes (e.g. Steinernema feltiae), andentomopathogenic viruses (e.g. Cydia pomonella granulovirus). Otherexamples of entomopathogenic organisms include, but are not limited to,baculoviruses, protozoa, and Microsporidia. For the avoidance of doubt,biopesticides are active ingredients.

The term “cycloalkenyl” means a monocyclic or polycyclic, unsaturated(at least one carbon-carbon double bond) substituent consisting ofcarbon and hydrogen, for example, cyclobutenyl, cyclopentenyl,cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl,hexahydronaphthyl, and octahydronaphthyl.

The term “cycloalkenyloxy” means a cycloalkenyl further consisting of acarbon-oxygen single bond, for example, cyclobutenyloxy,cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.

The term “cycloalkyl” means a monocyclic or polycyclic, saturatedsubstituent consisting of carbon and hydrogen, for example, cyclopropyl,cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, anddecahydronaphthyl.

The term “cycloalkoxy” means a cycloalkyl further consisting of acarbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy,cyclopentyloxy, norbornyloxy, and bicyclo[2.2.2]octyloxy.

The term “halo” means fluoro, chloro, bromo, and iodo.

The term “haloalkoxy” means an alkoxy further consisting of, from one tothe maximum possible number of identical or different, halos, forexample, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy,chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethoxy, andpentafluoroethoxy.

The term “haloalkyl” means an alkyl further consisting of, from one tothe maximum possible number of, identical or different, halos, forexample, fluoromethyl, trifluoromethyl, 2,2-difluoropropyl,chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.

The term “heterocyclyl” means a cyclic substituent that may be aromatic,fully saturated, or partially or fully unsaturated, where the cyclicstructure contains at least one carbon and at least one heteroatom,where said heteroatom is nitrogen, sulfur, or oxygen. Examples are:

(1) aromatic heterocyclyl substituents aromatic heterocyclylsubstituents include, but are not limited to, benzofuranyl,benzoimidazolyl, benzoisothiazolyl, benzoisoxazolyl, benzothienyl,benzothiazolyl, benzothiophenyl, benzoxazolyl, cinnolinyl, furanyl,imidazolyl, imidazolylpyridinyl, indazolyl, indolyl, isoindolyl,isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl,oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl,pyrazolopyridinyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl,pyrrolopyridinyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl,thiadiazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl,[1,2,4]triazolo[1,5-c]pyrimidinyl, and triazolyl;

(2) fully saturated heterocyclyl substituents include, but are notlimited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl,tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl,tetrahydrothiophenyl-oxide, and tetrahydrothiophenyl-dioxide;

(3) partially or fully unsaturated heterocyclyl substituents include,but are not limited to, 2,3-dihydro-1H-imidazolonyl,4,5-dihydro-isoxazolyl, 4,5-dihydro-oxazolyl, 2,3-dihydrophthalazinyl,2,3-dihydrophthalazine-1,4-dionyl, 4,5-dihydro-1H-pyrazolyl,2,3-dihydro-[1,3,4]-oxadiazolyl, 2,5-dioxoimidazolidinyl,2,4-dioxo-1,3-diazaspiro[4.4]nonanylisoxazolidinonyl, indolinyl,imidazolidinonyl, isoxazolidinonyl, oxazolidinonyl,pyrimidine-2,4(1H,3H)-dionyl, pyrrolidinonyl,1,2,3,4-tetrahydro-pyrimidinyl, 1,2,3,4-tetrahydro-quinolinyl, andthioxothiazolidinonyl; and

(4) Additional examples of heterocyclyls include the following:

The term “locus” means a habitat, breeding ground, plant, seed, soil,material, or environment, in which a pest is growing, may grow, or maytraverse. For example, a locus may be: where crops, trees, fruits,cereals, fodder species, vines, turf, and/or ornamental plants, aregrowing; where domesticated animals are residing; the interior orexterior surfaces of buildings (such as places where grains are stored);the materials of construction used in buildings (such as impregnatedwood); and the soil around buildings.

The phrase “MoA Material” means an active ingredient having a mode ofaction (“MoA”) as indicated in IRAC MoA Classification v. 7.3, locatedat irac-online.org., which describes the following groups.

(1) Acetylcholinesterase (AChE) inhibitors, includes the followingactive ingredients alanycarb, aldicarb, bendiocarb, benfuracarb,butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan,ethiofencarb, fenobucarb, formetanate, furathiocarb, isoprocarb,methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, propoxur,thiodicarb, thiofanox, triazamate, trimethacarb, XMC, xylylcarb,acephate, azamethiphos, azinphos-ethyl, azinphos-methyl, cadusafos,chlorethoxyfos, chlorfenvinphos, chlormephos, chlorpyrifos,chlorpyrifos-methyl, coumaphos, cyanophos, demeton-S-methyl, diazinon,dichlorvos/DDVP, dicrotophos, dimethoate, dimethylvinphos, disulfoton,EPN, ethion, ethoprophos, famphur, fenamiphos, fenitrothion, fenthion,fosthiazate, heptenophos, imicyafos, isofenphos, isopropylO-(methoxyaminothio-phosphoryl) salicylate, isoxathion, malathion,mecarbam, methamidophos, methidathion, mevinphos, monocrotophos, naled,omethoate, oxydemeton-methyl, parathion, parathion-methyl, phenthoate,phorate, phosalone, phosmet, phosphamidon, phoxim, pirimiphos-methyl,profenofos, propetamphos, prothiofos, pyraclofos, pyridaphenthion,quinalphos, sulfotep, tebupirimfos, temephos, terbufos,tetrachlorvinphos, thiometon, triazophos, trichlorfon, vamidothion.

(2) GABA-gated chloride channel antagonists, includes the followingactive ingredients chlordane, endosulfan, ethiprole, and fipronil.

(3) Sodium channel modulators, includes the following active ingredientsacrinathrin, allethrin, d-cis-trans allethrin, d-trans allethrin,bifenthrin, bioallethrin, bioallethrin S-cyclopentenyl, bioresmethrin,cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin,lambda-cyhalothrin, gamma-cyhalothrin, cypermethrin, alpha-cypermethrin,beta-cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin[(1R)-trans-isomers], deltamethrin, empenthrin [(EZ)-(1R)-isomers],esfenvalerate, etofenprox, fenpropathrin, fenvalerate, flucythrinate,flumethrin, tau-fluvalinate, halfenprox, imiprothrin, kadethrin,permethrin, phenothrin [(1R)-trans-isomer], prallethrin, pyrethrins(pyrethrum), resmethrin, silafluofen, tefluthrin, tetramethrin,tetramethrin [(1R)-isomers], tralomethrin, and transfluthrin, andmethoxychlor.

(4) Nicotinic acetylcholine receptor (nAChR) agonists, includes thefollowing active ingredients

-   -   (4A) acetamiprid, clothianidin, dinotefuran, imidacloprid,        nitenpyram, thiacloprid, thiamethoxam,    -   (4B) nicotine,    -   (4C) sulfoxaflor,    -   (4D) flupyradifurone,    -   (4E) triflumezopyrim and dicloromezotiaz.

(5) Nicotinic acetylcholine receptor (nAChR) allosteric activators,includes the following active ingredients spinetoram and spinosad.

(6) Chloride channel activators, includes the following activeingredients abamectin, emamectin benzoate, lepimectin, and milbemectin.

(7) Juvenile hormone mimics, includes the following active ingredientshydroprene, kinoprene, methoprene, fenoxycarb, and pyriproxyfen.

(8) Miscellaneous nonspecific (multi-site) inhibitors, includes thefollowing active ingredients methyl bromide, chloropicrin, sulfurylfluoride, borax, and tartar emetic.

(9) Modulators of Chordotonal Organs, includes the following activeingredients pymetrozine and flonicamid.

(10) Mite growth inhibitors, includes the following active ingredientsclofentezine, hexythiazox, diflovidazin, and etoxazole.

(11) Microbial disruptors of insect midgut membranes, includes thefollowing active ingredients Bacillus thuringiensis subsp. Israelensis,Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp.Kurstaki, Bacillus thuringiensis subsp. tenebrionenis, Bt crop proteins(Cry1Ab, Cry1Ac, Cry1Fa, Cry1A.105, Cry2Ab, Vip3A, mCry3A, Cry3Ab,Cry3Bb, Cry34Ab1/Cry35Ab1), and Bacillus sphaericus.

(12) Inhibitors of mitochondrial ATP synthase, includes the followingactive ingredients tetradifon, propargite, azocyclotin, cyhexatin,fenbutatin oxide, and diafenthiuron.

(13) Uncouplers of oxidative phosphorylation via disruption of theproton gradient, includes the following active ingredients chlorfenapyr,DNOC, and sulfluramid.

(14) Nicotinic acetylcholine receptor (nAChR) channel blockers, includesthe following active ingredients bensultap, cartap hydrochloride,thiocyclam, and thiosultap-sodium.

(15) Inhibitors of chitin biosynthesis, type 0, includes the followingactive ingredients bistrifluron, chlorfluazuron, diflubenzuron,flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron,noviflumuron, teflubenzuron, and triflumuron.

(16) Inhibitors of chitin biosynthesis, type 1, includes the followingactive ingredient buprofezin.

(17) Moulting disruptor, Dipteran, includes the following activeingredient cyromazine.

(18) Ecdysone receptor agonists, includes the following activeingredients chromafenozide, halofenozide, methoxyfenozide, andtebufenozide.

(19) Octopamine receptor agonists, includes the following activeingredient amitraz.

(20) Mitochondrial complex III electron transport inhibitors, includesthe following active ingredients hydramethylnon, acequinocyl, andfluacrypyrim.

(21) Mitochondrial complex I electron transport inhibitors, includes thefollowing active ingredients fenazaquin, fenpyroximate, pyrimidifen,pyridaben, tebufenpyrad, tolfenpyrad, and rotenone.

(22) Voltage-dependent sodium channel blockers, includes the followingactive ingredients indoxacarb and metaflumizone.

(23) Inhibitors of acetyl CoA carboxylase, includes the following activeingredients spirodiclofen, spiromesifen, and spirotetramat.

(24) Mitochondrial complex IV electron transport inhibitors, includesthe following active ingredients, aluminium phosphide, calciumphosphide, phosphine, zinc phosphide, and cyanide.

(25) Mitochondrial complex II electron transport inhibitors, includesthe following active ingredients cyenopyrafen and cyflumetofen. and

(28) Ryanodine receptor modulators, includes the following activeingredients chlorantraniliprole, cyantraniliprole, and flubendiamide.

Groups 26 and 27 are unassigned in this version of the classificationscheme. Additionally, there is a Group UN that contains activeingredients of unknown or uncertain mode of action. This group includesthe following active ingredients, azadirachtin, benzoximate, bifenazate,bromopropylate, chinomethionat, cryolite, dicofol, pyridalyl, andpyrifluquinazon.

The term “pest” means an organism that is detrimental to humans, orhuman concerns (such as, crops, food, livestock, etc.), where saidorganism is from Phyla Arthropoda, Mollusca, or Nematoda. Particularexamples are ants, aphids, bed bugs, beetles, bristletails,caterpillars, cockroaches, crickets, earwigs, fleas, flies,grasshoppers, grubs, hornets, killer bees, leafhoppers, lice, locusts,maggots, mites, moths, nematodes, planthoppers, psyllids, sawflies,scales, silverfish, slugs, snails, spiders, springtails, stink bugs,symphylans, termites, thrips, ticks, wasps, whiteflies, and wireworms.

Additional examples are pests in

(1) Subphyla Chelicerata, Myriapoda, and Hexapoda.

(2) Classes of Arachnida, Symphyla, and Insecta.

(3) Order Anoplura. A non-exhaustive list of particular genera includes,but is not limited to, Haematopinus spp., Hoplopleura spp., Linognathusspp., Pediculus spp., Polyplax spp., Solenopotes spp., andNeohaematopinis spp. A non-exhaustive list of particular speciesincludes, but is not limited to, Haematopinus asini, Haematopinus suis,Linognathus setosus, Linognathus ovillus, Pediculus humanus capitis,Pediculus humanus humanus, and Pthirus pubis.

(4) Order Coleoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Acanthoscelides spp., Agriotes spp.,Anthonomus spp., Apion spp., Apogonia spp., Araecerus spp., Aulacophoraspp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp.,Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp.,Cyclocephala spp., Diabrotica spp., Dinoderus spp., Gnathocerus spp.,Hemicoelus spp., Heterobostruchus spp., Hypera spp., Ips spp., Lyctusspp., Megascelis spp., Meligethes spp., Mezium spp., Niptus spp.,Otiorhynchus spp., Pantomorus spp., Phyllophaga spp., Phyllotreta spp.,Ptinus spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp.,Scolytus spp., Sphenophorus spp., Sitophilus spp., Tenebrio spp., andTribolium spp. A non-exhaustive list of particular species includes, butis not limited to, Acanthoscelides obtectus, Agrilus planipennis,Ahasverus advena, Alphitobius diaperinus, Anoplophora glabripennis,Anthonomus grandis, Anthrenus verbasci, Anthrenus falvipes, Ataeniusspretulus, Atomaria linearis, Attagenus unicolor, Bothynoderespunctiventris, Bruchus pisorum, Callosobruchus maculatus, Carpophilushemipterus, Cassida vittata, Cathartus quadricollis, Cerotomatrifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi, Conoderusscalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida,Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestes pusillus,Cryptolestes turcicus, Cylindrocopturus adspersus, Deporaus marginatus,Dermestes lardarius, Dermestes maculatus, Epilachna varivestis,Euvrilletta peltata, Faustinus cubae, Hylobius pales, Hylotrupesbajulus, Hypera postica, Hypothenemus hampei, Lasioderma serricorne,Leptinotarsa decemlineata, Limonius canus, Liogenys fuscus, Liogenyssuturalis, Lissorhoptrus oryzophilus, Lophocateres pusillus, Lyctusplanicollis, Maecolaspis joliveti, Melanotus communis, Meligethesaeneus, Melolontha melolontha, Necrobia rufipes, Oberea brevis, Oberealinearis, Oryctes rhinoceros, Oryzaephilus mercator, Oryzaephilussurinamensis, Oulema melanopus, Oulema oryzae, Phyllophaga cuyabana,Polycaon stoutti, Popillia japonica, Prostephanus truncatus, Rhyzoperthadominica, Sitona lineatus, Sitophilus granarius, Sitophilus oryzae,Sitophilus zeamais, Stegobium paniceum, Tenebroides mauritanicus,Tribolium castaneum, Tribolium confusum, Trogoderma granarium,Trogoderma variabile, Xestobium rufovillosum, and Zabrus tenebrioides.

(5) Order Dermaptera. A non-exhaustive list of particular speciesincludes, but is not limited to, Forficula auricularia.

(6) Order Blattaria. A non-exhaustive list of particular speciesincludes, but is not limited to, Blattella germanica, Blattellaasahinai, Blatta orientalis, Blatta lateralis, Parcoblattapennsylvanica, Periplaneta americana, Periplaneta australasiae,Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis,and Supella longipalpa.

(7) Order Diptera. A non-exhaustive list of particular genera includes,but is not limited to, Aedes spp., Agromyza spp., Anastrepha spp.,Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp.,Cochliomyia spp., Contarinia spp., Culex spp., Culicoides spp.,Dasineura spp., Delia spp., Drosophila spp., Fannia spp., Hylemya spp.,Liriomyza spp., Musca spp., Phorbia spp., Pollenia spp., Psychoda spp.,Simulium spp., Tabanus spp., and Tipula spp. A non-exhaustive list ofparticular species includes, but is not limited to, Agromyza frontella,Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqua, Bactroceracucurbitae, Bactrocera dorsalis, Bactrocera invadens, Bactrocera zonata,Ceratitis capitata, Dasineura brassicae, Delia platura, Fanniacanicularis, Fannia scalaris, Gasterophilus intestinalis, Gracilliaperseae, Haematobia irritans, Hypoderma lineatum, Liriomyza brassicae,Melophagus ovinus, Musca autumnalis, Musca domestica, Oestrus ovis,Oscinella frit, Pegomya betae, Piophila casei, Psila rosae, Rhagoletiscerasi, Rhagoletis pomonella, Rhagoletis mendax, Sitodiplosis mosellana,and Stomoxys calcitrans.

(8) Order Hemiptera. A non-exhaustive list of particular generaincludes, but is not limited to, Adelges spp., Aulacaspis spp.,Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspisspp., Chrysomphalus spp., Coccus spp., Empoasca spp., Euschistus spp.,Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp.,Nephotettix spp., Nezara spp., Nilaparvata spp., Philaenus spp.,Phytocoris spp., Piezodorus spp., Planococcus spp., Pseudococcus spp.,Rhopalosiphum spp., Saissetia spp., Therioaphis spp., Toumeyella spp.,Toxoptera spp., Trialeurodes spp., Triatoma spp., and Unaspis spp. Anon-exhaustive list of particular species includes, but is not limitedto, Acrosternum hilare, Acyrthosiphon pisum, Aleyrodes proletella,Aleurodicus dispersus, Aleurothrixus floccosus, Amrasca biguttulabiguttula, Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphispomi, Aulacorthum solani, Bactericera cockerelli, Bagrada hilaris,Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Boiseatrivittata, Brachycorynella asparagi, Brevennia rehi, Brevicorynebrassicae, Cacopsylla pyri, Cacopsylla pyricola, Calocoris norvegicus,Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertusfasciatus, Dichelops furcatus, Diuraphis noxia, Diaphorina citri,Dysaphis plantaginea, Dysdercus suturellus, Edessa meditabunda, Eriosomalanigerum, Eurygaster maura, Euschistus conspersus, Euschistus heros,Euschistus servus, Halyomorpha halys, Helopeltis antonii, Helopeltistheivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus,Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus,Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium,Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva frimbiolata,Megacopta cribraria, Metopolophium dirhodum, Mictis longicornis, Myzuspersicae, Nephotettix cincticeps, Neurocolpus longirostris, Nezaraviridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphi,Peregrinus maidis, Phylloxera vitifoliae, Physokermes piceae, Phytocoriscalifornicus, Phytocoris relativus, Piezodorus guildinii, Poecilocapsuslineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcusbrevipes, Quadraspidiotus perniciosus, Rhopalosiphum maidis,Rhopalosiphum padi, Saissetia oleae, Scaptocoris castanea, Schizaphisgraminum, Sitobion avenae, Sogatella furcifera, Trialeurodesvaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zuliaentrerriana.

(9) Order Hymenoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Acromyrmex spp., Atta spp., Camponotusspp., Diprion spp., Dolichovespula spp., Formica spp., Monomorium spp.,Neodiprion spp., Paratrechina spp., Pheidole spp., Pogonomyrmex spp.,Polistes spp., Solenopsis spp., Technomyrmex, spp., Tetramorium spp.,Vespula spp., Vespa spp., and Xylocopa spp. A non-exhaustive list ofparticular species includes, but is not limited to, Athalia rosae, Attatexana, Caliroa cerasi, Cimbex americana, Iridomyrmex humilis,Linepithema humile, Mellifera Scutellata, Monomorium minimum, Monomoriumpharaonis, Neodiprion sertifer, Solenopsis invicta, Solenopsis geminata,Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, Tapinomasessile, and Wasmannia auropunctata.

(10) Order Isoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Coptotermes spp., Cornitermes spp.,Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermesspp., Macrotermes spp., Marginitermes spp., Microcerotermes spp.,Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp., andZootermopsis spp. A non-exhaustive list of particular species includes,but is not limited to, Coptotermes acinaciformis, Coptotermescurvignathus, Coptotermes frenchi, Coptotermes formosanus, Coptotermesgestroi, Cryptotermes brevis, Heterotermes aureus, Heterotermes tenuis,Incisitermes minor, Incisitermes snyderi, Microtermes obesi,Nasutitermes corniger, Odontotermes formosanus, Odontotermes obesus,Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermesflavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermessantonensis, Reticulitermes speratus, Reticulitermes tibialis, andReticulitermes virginicus.

(11) Order Lepidoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Adoxophyes spp., Agrotis spp.,Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp.,Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp., Diatraeaspp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortynaspp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocolletisspp., Loxagrotis spp., Malacosoma spp., Nemapogon spp., Peridroma spp.,Phyllonorycter spp., Pseudaletia spp., Plutella spp., Sesamia spp.,Spodoptera spp., Synanthedon spp., and Yponomeuta spp. A non-exhaustivelist of particular species includes, but is not limited to, Achaeajanata, Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbiacuneana, Amyelois transitella, Anacamptodes defectaria, Anarsialineatella, Anomis sabulifera, Anticarsia gemmatalis, Archipsargyrospila, Archips rosana, Argyrotaenia citrana, Autographa gamma,Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capuareticulana, Carposina niponensis, Chlumetia transversa, Choristoneurarosaceana, Cnaphalocrocis medinalis, Conopomorpha cramerella, Corcyracephalonica, Cossus cossus, Cydia caryana, Cydia funebrana, Cydiamolesta, Cydia nigricana, Cydia pomonella, Darna diducta, Diaphanianitidalis, Diatraea saccharalis, Diatraea grandiosella, Earias insulana,Earias vittella, Ecdytolopha aurantianum, Elasmopalpus lignosellus,Ephestia cautella, Ephestia elutella, Ephestia kuehniella, Epinotiaaporema, Epiphyas postvittana, Erionota thrax, Estigmene acrea,Eupoecilia ambiguella, Euxoa auxiliaris, Galleria mellonella, Grapholitamolesta, Hedylepta indicata, Helicoverpa armigera, Helicoverpa zea,Heliothis virescens, Hellula undalis, Keiferia lycopersicella,Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella,Lobesia botrana, Loxagrotis albicosta, Lymantria dispar, Lyonetiaclerkella, Mahasena corbetti, Mamestra brassicae, Manduca sexta, Marucatestulalis, Metisa plana, Mythimna unipuncta, Neoleucinodes elegantalis,Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydiavesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus,Pectinophora gossypiella, Peridroma saucia, Perileucoptera coffeella,Phthorimaea operculella, Phyllocnistis citrella, Phyllonorycterblancardella, Pieris rapae, Plathypena scabra, Platynota idaeusalis,Plodia interpunctella, Plutella xylostella, Polychrosis viteana, Praysendocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens,Rachiplusia nu, Scirpophaga incertulas, Sesamia inferens, Sesamianonagrioides, Setora nitens, Sitotroga cerealella, Sparganothispilleriana, Spodoptera exigua, Spodoptera frugiperda, Spodopteraeridania, Thecla basilides, Tinea pellionella, Tineola bisselliella,Trichoplusia ni, Tuta absoluta, Zeuzera coffeae, and Zeuzea pyrina.

(12) Order Mallophaga. A non-exhaustive list of particular generaincludes, but is not limited to, Anaticola spp., Bovicola spp.,Chelopistes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp.A non-exhaustive list of particular species includes, but is not limitedto, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistesmeleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthusstramineus, Menopon gallinae, and Trichodectes canis.

(13) Order Orthoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Melanoplus spp. and Pterophylla spp. Anon-exhaustive list of particular species includes, but is not limitedto, Acheta domesticus, Anabrus simplex, Gryllotalpa africana,Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla,Locusta migratoria, Microcentrum retinerve, Schistocerca gregaria, andScudderia furcata.

(14) Order Psocoptera. A non-exhaustive list of particular speciesincludes, but is not limited to, Liposcelis decolor, Liposcelisentomophila, Lachesilla quercus, and Trogium pulsatorium.

(15) Order Siphonaptera. A non-exhaustive list of particular speciesincludes, but is not limited to, Ceratophyllus gallinae, Ceratophyllusniger, Ctenocephalides canis, Ctenocephalides felis, and Pulex irritans.

(16) Order Thysanoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Caliothrips spp., Frankliniella spp.,Scirtothrips spp., and Thrips spp.

A non-exhaustive list of particular species includes, but is not limitedto, Frankliniella bispinosa, Frankliniella fusca, Frankliniellaoccidentalis, Frankliniella schultzei, Frankliniella tritici,Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothripscruentatus, Scirtothrips citri, Scirtothrips dorsalis, Taeniothripsrhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thripsorientalis, Thrips palmi, and Thrips tabaci.

(17) Order Thysanura. A non-exhaustive list of particular generaincludes, but is not limited to, Lepisma spp. and Thermobia spp.

(18) Order Acarina. A non-exhaustive list of particular genera includes,but is not limited to, Acarus spp., Aculops spp., Argus spp., Boophilusspp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp.,Ixodes spp., Oligonychus spp., Panonychus spp., Rhizoglyphus spp., andTetranychus spp. A non-exhaustive list of particular species includes,but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae,Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyommaamericanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentorvariabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini,Liponyssoides sanguineus, Notoedres cati, Oligonychus coffeae,Oligonychus ilicis, Ornithonyssus bacoti, Panonychus citri, Panonychusulmi, Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalussanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychusurticae, Tyrophagus longior, and Varroa destructor.

(19) Order Araneae. A non-exhaustive list of particular genera includes,but is not limited to, Loxosceles spp., Latrodectus spp., and Atrax spp.A non-exhaustive list of particular species includes, but is not limitedto, Loxosceles reclusa, Latrodectus mactans, and Atrax robustus.

(20) Class Symphyla. A non-exhaustive list of particular speciesincludes, but is not limited to, Scutigerella immaculata.

(21) Subclass Collembola. A non-exhaustive list of particular speciesincludes, but is not limited to, Bourletiella hortensis, Onychiurusarmatus, Onychiurus fimetarius, and Sminthurus viridis.

(22) Phylum Nematoda. A non-exhaustive list of particular generaincludes, but is not limited to, Aphelenchoides spp., Belonolaimus spp.,Criconemella spp., Ditylenchus spp., Globodera spp., Heterodera spp.,Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchusspp., and Radopholus spp. A non-exhaustive list of particular speciesincludes, but is not limited to, Dirofilaria immitis, Globodera pallida,Heterodera glycines, Heterodera zeae, Meloidogyne incognita, Meloidogynejavanica, Onchocerca volvulus, Pratylenchus penetrans, Radopholussimilis, and Rotylenchulus reniformis.

(23) Phylum Mollusca. A non-exhaustive list of particular speciesincludes, but is not limited to, Arion vulgaris, Cornu aspersum,Deroceras reticulatum, Limax flavus, Milax gagates, and Pomaceacanaliculata.

A particularly preferred pest group to control is sap-feeding pests.Sap-feeding pests, in general, have piercing and/or sucking mouthpartsand feed on the sap and inner plant tissues of plants. Examples ofsap-feeding pests of particular concern to agriculture include, but arenot limited to, aphids, leafhoppers, moths, scales, thrips, psyllids,mealybugs, stinkbugs, and whiteflies. Specific examples of Orders thathave sap-feeding pests of concern in agriculture include but are notlimited to, Anoplura and Hemiptera. Specific examples of Hemiptera thatare of concern in agriculture include, but are not limited to,Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Coccus spp.,Euschistus spp., Lygus spp., Macrosiphum spp., Nezara spp., andRhopalosiphum spp.

Another particularly preferred pest group to control is chewing pests.Chewing pests, in general, have mouthparts that allow them to chew onthe plant tissue including roots, stems, leaves, buds, and reproductivetissues (including, but not limited to flowers, fruit, and seeds).Examples of chewing pests of particular concern to agricultural include,but are not limited to, caterpillars, beetles, grasshoppers, andlocusts. Specific examples of Orders that have chewing pests of concernin agriculture include but are not limited to, Coleoptera andLepidoptera. Specific examples of Coleoptera that are of concern inagriculture include, but are not limited to, Anthonomus spp., Cerotomaspp., Chaetocnema spp., Colaspis spp., Cyclocephala spp., Diabroticaspp., Hypera spp., Phyllophaga spp., Phyllotreta spp., Sphenophorusspp., Sitophilus spp.

The phrase “pesticidally effective amount” means the amount of apesticide needed to achieve an observable effect on a pest, for example,the effects of necrosis, death, retardation, prevention, removal,destruction, or otherwise diminishing the occurrence and/or activity ofa pest in a locus. This effect may come about when pest populations arerepulsed from a locus, pests are incapacitated in, or around, a locus,and/or pests are exterminated in, or around, a locus. Of course, acombination of these effects can occur. Generally, pest populations,activity, or both are desirably reduced more than fifty percent,preferably more than 90 percent, and most preferably more than 99percent. In general, a pesticidally effective amount, for agriculturalpurposes, is from about 0.0001 grams per hectare to about 5000 grams perhectare, preferably from about 0.0001 grams per hectare to about 500grams per hectare, and it is even more preferably from about 0.0001grams per hectare to about 50 grams per hectare.

DETAILED DESCRIPTION OF THIS DISCLOSURE

This document discloses molecules of Formula One

wherein:

(A) R¹ is selected from the group consisting of H, F, Cl, Br, I, CN,NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl,(C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl,(C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl,(C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,(C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂;

(B) R² is selected from the group consisting of H, F, Cl, Br, I, CN,NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl,(C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl,(C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl,(C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,(C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂;

(C) R³ is selected from the group consisting of H, F, Cl, Br, I, CN,NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl,(C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl,(C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl,(C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,(C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂;

(D) R⁴ is selected from the group consisting of H, F, Cl, Br, I, CN,NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl,(C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl,(C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl,(C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,(C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂;

(E) R⁵ is selected from the group consisting of H, F, Cl, Br, I, CN,NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl,(C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl,(C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl,(C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,(C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂;

(F) R⁶ is selected from the group consisting of H and (C₁-C₆)alkyl;

(G) R⁷ is selected from the group consisting of H, F, Cl, Br, and I;

(H) R⁸ is selected from the group consisting of F, Cl, Br, and I;

(I) R⁹ is selected from the group consisting of H and (C₁-C₆)alkyl;

(J) Q¹ is selected from the group consisting of O and S;

(K) Q² is selected from the group consisting of O and S;

(L) R¹⁰ is selected from the group consisting of H, (C₁-C₆)alkyl,(C₂-C₆)alkenyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkyl(C₁-C₆)alkoxy,C(═O)(C₁-C₆)alkyl, and (C₁-C₆)alkoxyC(═O)(C₁-C₆)alkyl;

(M) R¹¹ is selected from the group consisting of H, F, Cl, Br, I, CN,NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl,(C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl,(C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl,(C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,(C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂;

(N) R¹² is selected from the group consisting of H, F, Cl, Br, I, CN,NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl,(C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl,(C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl,(C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,(C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂;

(O) X¹ is selected from the group consisting of

-   -   (1) N,    -   (2) NO, and    -   (3) CR¹³,    -   wherein R¹³ is selected from the group consisting of H, F, Cl,        Br, I, CN, NH₂, NO₂, CHO, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,        (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl,        (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,        (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy,        S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,        S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,        (C₁-C₆)alkyl-S(O)₂NH₂, (C₁-C₆)haloalkyl-S(O)₂NH₂, and triazolyl;

(P) X² is selected from the group consisting of

-   -   (1) N,    -   (2) NO, and    -   (3) CR¹⁴,    -   wherein R¹⁴ is selected from the group consisting of H, F, Cl,        Br, I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,        (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl,        (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,        (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy,        S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,        S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,        (C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂;

(Q) X³ is selected from the group consisting of N(R¹⁵)(substituted orunsubstituted phenyl), N(R¹⁵)(substituted or unsubstitutedheterocyclyl), and substituted or unsubstituted heterocyclyl,

-   -   (a) wherein said R¹⁵ is selected from the group consisting of H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)haloalkyl,        (C₁-C₆)alkyl(C₁-C₆)alkoxy, C(═O)(C₁-C₆)alkyl, and        (C₁-C₆)alkoxyC(═O)(C₁-C₆)alkyl,    -   (b) wherein said substituted phenyl and substituted heterocyclyl        has one or more substituents selected from the group consisting        of F, Cl, Br, I, H, CN, CHO, NHOH, NO, NO₂, OH, (C₁-C₆)alkoxy,        (C₁-C₆)alkyl, (C₁-C₆)alkylphenyl, (C₁-C₆)alkyl-S(O)₂NH₂,        (C₁-C₆)haloalkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkyl-S(O)₂NH₂,        (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₂-C₆)haloalkenyl,        (C₃-C₆)cycloalkenyl, (C₃-C₆)cycloalkyl, (C₃-C₆)halocycloalkenyl,        (C₃-C₆)halocycloalkyl,        (C₁-C₆)alkyl((C₁-C₆)alkyl)(═NO(C₁-C₆)alkyl),        C(═NO(C₁-C₆)alkyl)(C₁-C₆)alkyl, C(O)(C₁-C₆)alkyl,        C(O)NH(C₁-C₆)alkyl, C(O)NHphenyl, C(O)O(C₁-C₆)alkyl,        CH(═NO(C₁-C₆)alkyl), imidazolyl,        N((C₁-C₆)alkyl)(C(O)(C₁-C₆)alkyl),        N((C₁-C₆)alkyl)(C(O)(C₁-C₆)alkyl-O(C₁-C₆)alkyl),        N((C₁-C₆)alkyl)(C(O)(C₁-C₆)haloalkyl),        N((C₁-C₆)alkyl)(C(O)O(C₁-C₆)alkyl), N((C₁-C₆)alkyl)₂,        N(C(O)O(C₁-C₆)alkyl)₂, N═CH— phenyl,        NH((C₁-C₆)alkylC(O)(C₁-C₆)alkyl), NH(C(O)(C₁-C₆)alkyl),        NH(C(O)(C₂-C₆)alkenyl), NH(C(O)(C₃-C₆)cycloalkyl),        NH(C₁-C₆)alkyl, NH(C₁-C₆)alkenyl, NH(C₁-C₆)alkynyl,        NH(C₁-C₆)alkylphenyl, NH(S(O)₂(C₁-C₆)alkyl), NH₂,        NHC(O)(C₁-C₆)alkyl, NHC(O)(C₁-C₆)alkylphenyl,        NHC(O)(C₁-C₆)alkylphenyl, NHC(O)(C₁-C₆)haloalkyl,        NHC(O)(C₂-C₆)alkenyl, NH—C(O)O(C₁-C₆)alkyl, oxazolyl, phenyl,        pyrazolyl, pyridinyl, S(═NCN)((C₁-C₆)alkyl), S(C₁-C₆)alkyl,        S(C₁-C₆)haloalkyl, S(O)(═NCN)((C₁-C₆)alkyl), S(O)(C₁-C₆)alkyl,        S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)alkyl, S(O)₂(C₁-C₆)haloalkyl,        SCN, thiazolyl, thienyl, and triazolyl,    -   wherein each alkoxy, alkyl, haloalkoxy, haloalkyl, alkenyl,        alkynyl, haloalkenyl, cycloalkenyl, cycloalkyl,        halocycloalkenyl, halocycloalkyl, imidazolyl, phenyl, pyrazolyl,        pyridinyl, thiazolyl, thienyl, and triazolyl, may be optionally        substituted with one or more substituents selected from the        group consisting of F, Cl, Br, I, CN, OH, NH(C₁-C₆)alkyl,        NH(C₃-C₆)cycloalkylCH₂O(C₁-C₆)alkyl,        NH(C₃-C₆)cycloalkylCH₂O(C₁-C₆)haloalkyl, NHCH₂(C₃-C₆)cycloalkyl,        NH₂, NO₂, oxo, (C₁-C₆)alkyl, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, and        C(O)O—(C₁-C₆)alkyl; and

N-oxides, agriculturally acceptable acid addition salts, saltderivatives, solvates, ester derivatives, crystal polymorphs, isotopes,resolved stereoisomers, and tautomers, of the molecules of Formula One.

The molecules of Formula One may exist in different geometric or opticalisomeric or different tautomeric forms. One or more centers of chiralitymay be present in which case molecules of Formula One may be present aspure enantiomers, mixtures of enantiomers, pure diastereomers ormixtures of diastereomers. It will be appreciated by those skilled inthe art that one stereoisomer may be more active than the otherstereoisomers. Individual stereoisomers may be obtained by knownselective synthetic procedures, by conventional synthetic proceduresusing resolved starting materials, or by conventional resolutionprocedures. There may be double bonds present in the molecule, in whichcase compounds of Formula One may exist as single geometric isomers (cisor trans, E or Z) or mixtures of geometric isomers (cis and trans, E andZ). Centers of tautomerisation may be present. This disclosure coversall such isomers, tautomers, and mixtures thereof, in all proportions.

In another embodiment the molecules of Formula One, the carboxamido, andthe phenyl, which are bonded to the cyclopropane, are in the R,Rconfiguration. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹,Q², X¹, X², and X³.

In another embodiment R¹ is selected from the group consisting of H, F,or Cl. This embodiment may be used in combination with the otherembodiments of R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q²,X¹, X², and X³.

In another embodiment R² is selected from the group consisting of H, F,Cl, Br, CH₃, and CF₃. This embodiment may be used in combination withthe other embodiments of R¹, R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹²,Q¹, Q², X¹, X², and X³.

In another embodiment R³ is selected from the group consisting of H, F,Cl, Br, CH₃, CF₃, and OCF₃. This embodiment may be used in combinationwith the other embodiments of R¹, R², R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹,R¹², Q¹, Q², X¹, X², and X³.

In another embodiment R⁴ is selected from the group consisting of H, F,Cl, Br, CH₃, and CF₃. This embodiment may be used in combination withthe other embodiments of R¹, R², R³, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹²,Q¹, Q², X¹, X², and X³.

In another embodiment R⁵ is selected from the group consisting of H andCl. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q²,X¹, X², and X³.

In another embodiment R⁶ is H. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁷, R, R⁹,R¹⁰, R¹¹, R¹², Q¹, Q², X¹, X², and X³.

In another embodiment R⁷ is selected from the group consisting of Cl andBr. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q²,X¹, X², and X³.

In another embodiment R⁸ is selected from the group consisting of Cl andBr. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q²,X¹, X², and X³.

In another embodiment R⁹ is H. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁸, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, X², and X³.

In another embodiment R¹⁰ is H or CH₃. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁸, R⁹, R¹¹, R¹², Q¹, Q², X¹, X², and X³.

In another embodiment R¹¹ is selected from the group consisting of H, F,Cl, and CH₃. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹², Q¹, Q², X¹,X², and X³.

In another embodiment R¹² is selected from the group consisting of H andCl. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, Q¹, Q², X¹,X², and X³.

In another embodiment Q¹ is O. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁸, R⁹, R¹⁰, R¹¹, R¹², Q², X¹, X², and X³.

In another embodiment Q² is selected from the group consisting of 0 andS. This embodiment may be used in combination with the other embodimentsof R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, X¹, X², andX³.

In another embodiment X¹ is selected from the group consisting of N, NO,and CR¹³. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹,Q², X², and X³.

In another embodiment R¹³ is selected from the group consisting of H, F,Cl, Br, I, CN, CH₃, CF₃, OCH₃, OCF₃, SCH₃, S(O)CH₃, S(O)₂CH₃, andtriazolyl. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹,Q², X², and X³.

In another embodiment X² is selected from the group consisting of N andCR¹⁴. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹, R¹², Q¹, Q²,X¹, and X³.

In another embodiment R¹⁴ is selected from the group consisting of H, F,Cl, and OCH₃. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹,Q², X¹, and X³.

In another embodiment X³ is selected from the group consisting of

wherein:

-   -   (a) R¹⁵ is selected from the group consisting of H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)haloalkyl,        (C₁-C₆)alkyl(C₁-C₆)alkoxy, C(═O)(C₁-C₆)alkyl, and        (C₁-C₆)alkoxyC(═O)(C₁-C₆)alkyl;    -   (b) X⁴ is selected from the group consisting of        -   (i) N,        -   (ii) NO, and        -   (iii) CR¹⁶,        -   wherein R¹⁶ is selected from the group consisting of H, F,            Cl, Br, I, CN, NH₂, NO₂, CHO, (C₁-C₆)alkyl,            (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl,            (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl,            (C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl,            (C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl,            S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl,            S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl, CO(C₁-C₆)alkyl,            CH(═NO(C₁-C₆)alkyl), C(═NO(C₁-C₆)alkyl)(C₁-C₆)alkyl,            (C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂,        -   wherein each alkyl, cycloalkyl, alkenyl, cycloalkenyl,            alkynyl, alkoxy, haloalkyl, halocycloalkyl, haloalkenyl,            halocycloalkenyl, and haloalkoxy, may be optionally            substituted with one or more substituents selected from the            group consisting of F, Cl, Br, I, CN, OH, NH₂, NO₂, oxo,            (C₁-C₆)alkyl, (C₁-C₆)alkoxy, and C(O)O—(C₁-C₆)alkyl;    -   (c) X⁵ is selected from the group consisting of        -   (i) N,        -   (ii) NO, and        -   (iii) CR¹⁷,        -   wherein R¹⁷ is selected from the group consisting of H, F,            Cl, Br, I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,            (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl,            (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,            (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl,            (C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl,            S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl,            S(O)₂(C₁-C₆)haloalkyl, C(O)O(C₁-C₆)alkyl,            (C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂;    -   (d) X⁶ is selected from the group consisting of        -   (i) N,        -   (ii) NO, and        -   (iii) and CR¹⁸,        -   wherein R¹⁸ is selected from the group consisting of H, F,            Cl, Br, I, CN, NO₂, OH, NH₂, SCN, CHO, (C₁-C₆)alkyl,            (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)haloalkyl,            (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, NH(C₁-C₆)alkyl,            N((C₁-C₆)alkyl)₂, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl,            S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl,            S(O)₂(C₁-C₆)haloalkyl, CO(C₁-C₆)alkyl, CONH(C₁-C₆)alkyl,            NHCO(C₁-C₆)alkyl, N(C₁-C₆)alkyl-CO(C₁-C₆)alkyl,            NHCO(C₂-C₆)alkenyl, NHCO(C₃-C₆)cycloalkyl,            NHCO(C₁-C₆)haloalkyl, N(C₁-C₆)alkyl-CO(C₁-C₆)haloalkyl,            NHCO(C₁-C₆)alkylphenyl, NH—C(O)O(C₁-C₆)alkyl,            N(C₁-C₆)alkyl-C(O)O(C₁-C₆)alkyl, CH(═NO(C₁-C₆)alkyl),            C(═NO(C₁-C₆)alkyl)(C₁-C₆)alkyl, phenyl, pyrazolyl,            imidazolyl, and triazolyl,        -   wherein each alkyl, alkenyl, alkynyl, haloalkyl, alkoxy,            haloalkoxy, halocycloalkyl, cycloalkyl, phenyl, imidazolyl,            and triazolyl, may be optionally substituted with one or            more substituents selected from the group consisting of F,            Cl, Br, I, CN, OH, NH₂, NO₂, oxo, (C₁-C₆)alkyl,            (C₁-C₆)alkoxy, and C(O)O—(C₁-C₆)alkyl;    -   (e) X⁷ is selected from the group consisting of        -   (i) N,        -   (ii) NO, and        -   (iii) CR¹⁹,        -   wherein R¹⁹ is selected from the group consisting of H, F,            Cl, Br, I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,            (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl,            (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,            (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl,            (C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl,            S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl,            S(O)₂(C₁-C₆)haloalkyl, C(O)O(C₁-C₆)alkyl,            (C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂;    -   (f) X⁸ is selected from the group consisting of        -   (i) N,        -   (ii) NO, and        -   (iii) CR²⁰,        -   wherein R²⁰ is selected from the group consisting of H, F,            Cl, Br, I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,            (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl,            (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,            (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl,            (C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl,            S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl,            S(O)₂(C₁-C₆)haloalkyl, C(O)O(C₁-C₆)alkyl,            (C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂;    -   (g) R²¹ is selected from the group consisting of H, F, Cl, Br,        I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,        (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl,        (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,        (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy,        S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,        S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,        (C₁-C₆)alkyl-S(O)₂NH₂, (C₁-C₆)haloalkyl-S(O)₂NH₂, phenyl,        pyridinyl, and thienyl,    -   wherein each alkyl, alkenyl, alkynyl, haloalkyl, alkoxy,        haloalkoxy, phenyl, imidazolyl, and triazolyl, may be optionally        substituted with one or more substituents selected from the        group consisting of F, Cl, Br, I, CN, OH, NH₂, NO₂, oxo,        (C₁-C₆)alkyl, (C₁-C₆)alkoxy, and C(O)O—(C₁-C₆)alkyl.    -   (h) R²² is selected from the group consisting of H, F, Cl, Br,        I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,        (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl,        (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,        (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy,        S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,        S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,        (C₁-C₆)alkyl-S(O)₂NH₂, (C₁-C₆)haloalkyl-S(O)₂NH₂, phenyl,        pyridinyl, and thienyl,        -   wherein each alkyl, alkenyl, alkynyl, haloalkyl, alkoxy,            haloalkoxy, phenyl, imidazolyl, and triazolyl, may be            optionally substituted with one or more substituents            selected from the group consisting of F, Cl, Br, I, CN, OH,            NH₂, NO₂, oxo, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, and            C(O)O—(C₁-C₆)alkyl.    -   (i) R²³ is selected from the group consisting of H, F, Cl, Br,        I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,        (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl,        (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,        (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy,        S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,        S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,        (C₁-C₆)alkyl-S(O)₂NH₂, (C₁-C₆)haloalkyl-S(O)₂NH₂, phenyl,        pyridinyl, and thienyl,        -   wherein each alkyl, alkenyl, alkynyl, haloalkyl, alkoxy,            haloalkoxy, phenyl, imidazolyl, and triazolyl, may be            optionally substituted with one or more substituents            selected from the group consisting of F, Cl, Br, I, CN, OH,            NH₂, NO₂, oxo, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, and            C(O)O—(C₁-C₆)alkyl.    -   (j) R²⁴ is selected from the group consisting of H, F, Cl, Br,        I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,        (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl,        (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,        (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy,        S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,        S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,        (C₁-C₆)alkyl-S(O)₂NH₂, (C₁-C₆)haloalkyl-S(O)₂NH₂, phenyl,        pyridinyl, and thienyl,        -   wherein each alkyl, alkenyl, alkynyl, haloalkyl, alkoxy,            haloalkoxy, phenyl, imidazolyl, and triazolyl, may be            optionally substituted with one or more substituents            selected from the group consisting of F, Cl, Br, I, CN, OH,            NH₂, NO₂, oxo, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, and            C(O)O—(C₁-C₆)alkyl.

This embodiment may be used in combination with the other embodiments ofR¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, and X².

In another embodiment X³ is selected from the group consisting of

This embodiment may be used in combination with the other embodiments ofR¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, and X².

In another embodiment X³ said substituted or unsubstituted heterocyclylis selected from the group consisting of indolyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, tetrazolyl, thiadiazolyl,thiazolyl, thienyl, triazinyl, [1,2,4]triazolo[1,5-c]pyrimidinyl,triazolyl, 2,3-dihydrophthalazine-1,4-dionyl, indolinyl, andpyrimidine-2,4(1H,3H)-dionyl, wherein substituents are selected from thegroup consisting of F, Cl, Br, I, H, CN, NH₂, NO₂, (C₁-C₆)alkoxy,(C₁-C₆)alkyl, (C₁-C₆)haloalkoxy, (C₁-C₆)haloalkyl, (C₂-C₆)haloalkenyl,(C₃-C₆)halocycloalkenyl, and (C₃-C₆)halocycloalkyl. This embodiment maybe used in combination with the other embodiments of R¹, R², R³, R⁴, R⁵,R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹, Q¹, Q², X¹, and X².

In another embodiment X³ said substituted or unsubstituted heterocyclylis selected from the group consisting of indolinyl, oxazolyl, pyridyl,and thiadiazolyl, wherein substituents are selected from the groupconsisting of F, Cl, Br, I, H, CN, NO₂, NH₂, (C₁-C₆)alkoxy,(C₁-C₆)alkyl, (C₁-C₆)haloalkoxy, (C₁-C₆)haloalkyl, (C₂-C₆)haloalkenyl,(C₃-C₆)halocycloalkenyl, and (C₃-C₆)halocycloalkyl. This embodiment maybe used in combination with the other embodiments of R¹, R², R³, R⁴, R⁵,R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, and X².

In another embodiment X³ is N(R¹⁵)(substituted or unsubstituted phenyl),

-   -   (a) wherein said R¹⁵ is selected from the group consisting of H,        and (C₁-C₆)alkyl,    -   (b) wherein said substituted phenyl has one or more substituents        selected from the group consisting of F, Cl, Br, I, CN, NO₂,        NH₂, (C₁-C₆)alkoxy, (C₁-C₆)alkyl, (C₁-C₆)haloalkoxy,        (C₁-C₆)haloalkyl, (C₂-C₆)haloalkenyl, (C₃-C₆)cycloalkenyl,        (C₃-C₆)cycloalkyl, (C₃-C₆)halocycloalkenyl, and        (C₃-C₆)halocycloalkyl. This embodiment may be used in        combination with the other embodiments of R¹, R², R³, R⁴, R⁵,        R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, and X².

In another embodiment R¹⁵ is selected from the group consisting of H,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH₂CH═CH₂, CH₂—C≡CH, and CH₂CF₃. This embodimentmay be used in combination with the other embodiments of R¹, R², R³, R⁴,R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, X², and X³.

In another embodiment X⁴ is selected from the group consisting of N andCR¹⁶. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹,Q², X¹, X², and X³.

In another embodiment R¹⁶ is selected from the group consisting of H, F,Cl, CN, NH₂, CH₃, CH₂CH₃, and CH₂(CH₃)₂. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, X², and X³.

In another embodiment X⁵ is selected from the group consisting of N, NO,and CR¹⁷. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R⁰, R¹¹, R¹², Q¹, Q²,X¹, X², and X³.

In another embodiment R¹⁷ is selected from the group consisting of H, F,Cl, and CN, NH₂. This embodiment may be used in combination with theother embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹²,Q¹, Q², X¹, X², and X³.

In another embodiment X⁶ is selected from the group consisting of N, NO,and CR¹⁸. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹,Q², X¹, X², and X³.

In another embodiment R¹⁸ is selected from the group consisting of H, F,Cl, CN, NO₂, NH₂, CH₃, CF₃, OCH₃, OCHCF₂, OCF₃, SCH₃, S(O)CH₃, S(O)₂CH₃,C(O)NHCH₃, and NHC(O)CH₃. This embodiment may be used in combinationwith the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰,R¹¹, R¹², Q¹, Q², X¹, X², and X³.

In another embodiment X⁷ is CR¹⁹. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, X², and X³.

In another embodiment R¹⁹ is selected from the group consisting of H, F,and NH₂. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹,Q², X¹, X², and X³.

In another embodiment X⁸ is CR²⁰. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, X², and X³.

In another embodiment R²⁰ is selected from the group consisting of H, F,Cl, and CH₃. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹,Q², X¹, X², and X³.

In another embodiment R²¹ is H. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, X², and X³.

In another embodiment R²² is H. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, X², and X³.

In another embodiment R²³ is H. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, X², and X³.

In another embodiment R²⁴ is H. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁸, R⁹, R¹⁰, R¹¹, R¹², Q¹, Q², X¹, X², and X³.

In another embodiment:

(A) R¹, R², R³, R⁴, R⁵, R¹¹, and R¹² are each independently selectedfrom the group consisting of H, F, Cl, Br, (C₁-C₆)alkyl,(C₁-C₆)haloalkyl, and (C₁-C₆)haloalkoxy;

(B) R⁶ and R⁹ are H;

(C) R⁷ is selected from the group consisting of Cl and Br;

(D) R⁸ is selected from the group consisting of Cl and Br;

(E) Q¹ and Q² are each independently selected from the group consistingof O and S;

(F) R¹⁰ is H;

(G) X¹ is selected from the group consisting of

-   -   (1) N,    -   (2) NO, and    -   (3) CR¹³,    -   wherein R¹³ is selected from the group consisting of H, F, Cl,        Br, I, CN, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl,        (C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl,        S(O)₂(C₁-C₆)alkyl, and triazolyl;

(H) X² is selected from the group consisting of

-   -   (1) N and    -   (2) CR¹⁴,    -   wherein R¹⁴ is selected from the group consisting of H, F, Cl,        and (C₁-C₆)alkoxy;

(I) X³ is selected from the group consisting of

wherein:

-   -   (a) R¹⁵ is selected from the group consisting of H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, and (C₁-C₆)haloalkyl;    -   (b) X⁴ is selected from the group consisting of        -   (i) N, and        -   (ii) CR¹⁶,        -   wherein R¹⁶ is selected from the group consisting of H, F,            Cl, CN, NH₂, and (C₁-C₆)alkyl;    -   (c) X⁵ is selected from the group consisting of        -   (i) N,        -   (ii) NO, and        -   (iii) CR¹⁷,        -   wherein R¹⁷ is selected from the group consisting of H, F,            Cl, NH₂, and CN;    -   (d) X⁶ is selected from the group consisting of        -   (i) N,        -   (ii) NO, and        -   (iii) and CR¹⁸,        -   wherein R¹⁸ is selected from the group consisting of H, F,            Cl, CN, NO₂, NH₂, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl,            (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl,            S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, CONH(C₁-C₆)alkyl, and            NHCO(C₁-C₆)alkyl;    -   (e) X⁷ is CR¹⁹,        -   wherein R¹⁹ is selected from the group consisting of H, NH₂,            and F;    -   (f) X⁸ is CR²⁰,        -   wherein R²⁰ is selected from the group consisting of H, F,            Cl, NH₂, and (C₁-C₆)alkyl; and    -   (g) R²¹, R²², R²³, and R²⁴ are H.

In another embodiment:

(A) R¹ is H;

(B) R² is selected from the group consisting of H, Cl, Br, (C₁-C₆)alkyl,and (C₁-C₆)haloalkyl;

(C) R³ is selected from the group consisting of H, F, Cl, Br,(C₁-C₆)alkyl, (C₁-C₆)haloalkyl, and (C₁-C₆)haloalkoxy;

(D) R⁴ is selected from the group consisting of H, Cl, Br, (C₁-C₆)alkyl,and (C₁-C₆)haloalkyl;

(E) R⁵ is selected from the group consisting of H and C₁;

(F) R⁶ is H;

(G) R⁷ is selected from the group consisting of Cl and Br;

(H) R⁸ is selected from the group consisting of Cl and Br;

(I) R⁹ is H;

(J) Q¹ is O;

(K) Q² is selected from the group consisting of 0 and S;

(L) R¹⁰ is H;

(M) R¹¹ is selected from the group consisting of H, F, Cl, and(C₁-C₆)alkyl;

(N) R¹² is selected from the group consisting of H and C₁;

(O) X¹ is selected from the group consisting of

-   -   (1) N,    -   (2) NO, and    -   (3) CR¹³,    -   wherein R¹³ is selected from the group consisting of H, F, Cl,        Br, I, CN, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl,        (C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl,        S(O)₂(C₁-C₆)alkyl, and triazolyl;

(P) X² is selected from the group consisting of

-   -   (1) N and    -   (2) CR¹⁴,    -   wherein R¹⁴ is selected from the group consisting of H, F, Cl,        and (C₁-C₆)alkoxy; and    -   (Q) X³ is selected from the group consisting of

wherein:

-   -   (a) R¹⁵ is selected from the group consisting of H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, and (C₁-C₆)haloalkyl;    -   (b) X⁴ is selected from the group consisting of        -   (i) N, and        -   (ii) CR¹⁶,        -   wherein R¹⁶ is selected from the group consisting of H, F,            Cl, CN, NH₂, and (C₁-C₆)alkyl;    -   (c) X⁵ is selected from the group consisting of        -   (i) N,        -   (ii) NO, and        -   (iii) CR¹⁷,        -   wherein R¹⁷ is selected from the group consisting of H, F,            Cl, NH₂, and CN;    -   (d) X⁶ is selected from the group consisting of        -   (i) N,        -   (ii) NO, and        -   (iii) and CR¹⁸,        -   wherein R¹⁸ is selected from the group consisting of H, F,            Cl, CN, NO₂, NH₂, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl,            (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl,            S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, CONH(C₁-C₆)alkyl, and            NHCO(C₁-C₆)alkyl;    -   (e) X⁷ is CR¹⁹,        -   wherein R¹⁹ is selected from the group consisting of H, NH₂,            and F;    -   (f) X⁸ is CR²⁰,        -   wherein R²⁰ is selected from the group consisting of H, F,            Cl, NH₂, and (C₁-C₆)alkyl; and    -   (g) R²¹, R²², R²³, and R²⁴ are H.        In another embodiment:

(A) R¹ is selected from the group consisting of H, F, or C₁;

(B) R² is selected from the group consisting of H, F, Cl, Br,(C₁-C₆)alkyl, and (C₁-C₆)haloalkyl;

(C) R³ is selected from the group consisting of H, F, Cl, Br,(C₁-C₆)alkyl, (C₁-C₆)haloalkyl, and (C₁-C₆)haloalkoxy;

(D) R⁴ is selected from the group consisting of H, F, Cl, Br,(C₁-C₆)alkyl, and (C₁-C₆)haloalkyl;

(E) R⁵ is selected from the group consisting of H, F, and C₁;

(F) R⁶ is H;

(G) R⁷ is selected from the group consisting of Cl and Br;

(H) R⁸ is selected from the group consisting of Cl and Br;

(I) R⁹ is H;

(3) Q¹ is O;

(K) Q² is selected from the group consisting of O and S;

(L) R¹⁰ is H;

(M) R¹¹ is selected from the group consisting of H, F, Cl, and(C₁-C₆)alkyl;

(N) R¹² is selected from the group consisting of H and Cl;

(O) X¹ is CR¹³,

-   -   wherein R¹³ is selected from the group consisting of H, F, Cl,        Br, I, CN, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, and        (C₁-C₆)haloalkoxy;

(P) X² is CR¹⁴,

-   -   wherein R¹⁴ is selected from the group consisting of H, F, Cl,        and (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, and        (C₁-C₆)haloalkoxy; and

(Q) X³ is

-   -   wherein:        -   R¹⁵ is selected from the group consisting of H,            (C₁-C₆)alkyl, (C₂-C₆)alkenyl, and (C₁-C₆)haloalkyl;        -   X⁴ is CR¹⁶ wherein R¹⁶ is selected from the group consisting            of H, F, Cl, NH₂, CN, NO₂, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl,            (C₁-C₆)alkoxy, and (C₁-C₆)haloalkoxy;        -   X⁵ is CR¹⁷ wherein R¹⁷ is selected from the group consisting            of H, F, Cl, NH₂, CN, NO₂, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl,            (C₁-C₆)alkoxy, and (C₁-C₆)haloalkoxy;        -   X⁶ is CR¹⁸ wherein R¹⁸ is selected from the group consisting            of H, F, Cl, NH₂, CN, NO₂, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl,            (C₁-C₆)alkoxy, and (C₁-C₆)haloalkoxy;        -   X⁷ is CR¹⁹ wherein R¹⁹ is selected from the group consisting            of H, F, Cl, NH₂, CN, NO₂, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl,            (C₁-C₆)alkoxy, and (C₁-C₆)haloalkoxy;        -   X⁸ is CR²⁰ wherein R²⁰ is selected from the group consisting            of H, F, Cl, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl,            (C₁-C₆)alkoxy, and (C₁-C₆)haloalkoxy.            Preparation of Cyclopropyl Carboxylic Acids

Stilbenes 1-1, wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁹ are as previouslydisclosed, may be treated with a base such as sodium hydroxide in thepresence of a carbene source such as chloroform or bromoform and a phasetransfer catalyst such as N-benzyl-N,N-diethylethanaminium chloride in apolar protic solvent such as water at temperatures from about 0° C. toabout 40° C. to provide diaryl cyclopropanes 1-2, wherein R¹, R², R³,R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are as previously disclosed (Scheme 1, stepa). Treatment of diaryl cyclopropanes 1-2 with a transition metal suchas ruthenium(III) chloride in the presence of a stoichiometric oxidantsuch as sodium periodate in a solvent mixture preferably water, ethylacetate, and acetonitrile at temperatures from about 0° C. to about 40°C. may provide cyclopropyl carboxylic acids 1-3, wherein R¹, R², R³, R⁴,R⁵, R⁶, R⁷, R⁸, and R⁹ are as previously disclosed (Scheme 1, step b).

Thiophene carbonyl 1.4-1, wherein R⁹ is as previously disclosed, may betreated with alkoxy benzyl phosphonate 2-2, wherein R¹, R², R⁴, R⁵ areas previously disclosed, in the presence of a base such as sodiummethoxide in a polar aprotic solvent such as N,N-dimethylformamide attemperatures from about −10° C. to about 80° C. to provide stilbene1.4-2, wherein R¹, R², R⁴, R⁵, R⁶, and R⁹ are as previously disclosed(Scheme 1.4, step a). Stilbene 1.4-2, wherein R¹, R², R⁴, R⁵, R⁶, and R⁹are as previously disclosed, may be treated with a base such as sodiumhydroxide in the presence of a carbene source such as chloroform orbromoform and a phase transfer catalyst such asN-benzyl-N,N-diethylethanaminium chloride in a polar protic solvent suchas water at temperatures from about 0° C. to about 40° C. to providethiophene cyclopropane 1.4-3, wherein R¹, R², R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹are as previously disclosed (Scheme 1.4, step b). Treatment of thiophenecyclopropane 1.4-3 with a transition metal such as ruthenium(III)chloride in the presence of a stoichiometric oxidant such as sodiumperiodate in a solvent mixture preferably water, ethyl acetate, andacetonitrile at temperatures from about 0° C. to about 40° C. mayprovide cyclopropyl carboxylic acid 1-3, wherein R³ is a (C₁-C₄)alkoxygroup and R¹, R², R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are as previously disclosed(Scheme 1.4, step c).

Phenyl carbonyls 1.7-1, wherein R¹, R², R³, R⁴, R⁵, and R⁶ are aspreviously disclosed, may be treated with alkoxy phosphonate 1.7-2 inthe presence of a base such as sodium hydride in a polar aprotic solventsuch as tetrahydrofuran at temperatures from about −10° C. to about 40°C. to provide stilbenes 1.7-3, wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁹are as previously disclosed (Scheme 1.7, step a). Stilbenes 1.7-3,wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁹ are as previously disclosed, maybe treated with a reducing agent such as diisobutylaluminum hydride(DIBAL) in a polar aprotic solvent such as toluene at temperatures fromabout −80° C. to about 0° C. to provide alcohols 1.7-4, wherein R¹, R²,R³, R⁴, R⁵, R⁶, and R⁹ are as previously disclosed (Scheme 1.7, step b).Alcohols 1.7-4, wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁹ are as previouslydisclosed, may be protected by treatment with 3,4-dihydro-2H-pyran inthe presence of an acid catalyst such as p-toluenesulfonic acid in apolar aprotic solvent such as diethyl ether at temperatures from about0° C. to about 40° C. to give protected stilbenes 1.7-5, wherein R¹, R²,R³, R⁴, R⁵, R⁶, and R⁹ are as previously disclosed (Scheme 1.7, step c).Protected stilbenes 1.7-5, wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁹ are aspreviously disclosed, may be treated with a base such as sodiumhydroxide in the presence of a carbene source such as chloroform orbromoform and a phase transfer catalyst such asN-benzyl-N,N-diethylethanaminium chloride in a polar protic solvent suchas water at temperatures from about 0° C. to about 40° C. to providecyclopropanes 1.7-7, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ areas previously disclosed (Scheme 1.7, step d). Cyclopropanes 1.7-6,wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are as previouslydisclosed, may be treated with an acid such as p-toluenesulfonic acid ina polar protic solvent such as methanol at temperatures from about 0° C.to about 40° C. to provide alcohols 1.7-7, wherein R¹, R², R³, R⁴, R⁵,R⁶, R⁷, R⁸, and R⁹ are as previously disclosed (Scheme 1.7, step e).Treatment of alcohols 1.7-7, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, andR⁹ are as previously disclosed, with an oxidant such as Jones reagent ina polar aprotic solvent such as acetone at temperatures from about −10°C. to about 40° C. to provide cyclopropyl carboxylic acids 1-3, whereinR¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are as previously disclosed(Scheme 1.7, step f).

Preparation of Stilbenes

Stilbenes 1-1 may be prepared by several different methods as outlinedin Scheme 2. Phenyl carbonyls 2-1, wherein R¹, R², R³, R⁴, R⁵, and R⁶are as previously disclosed, may be treated with alkoxy benzylphosphonates 2-2 in the presence of a base such as sodium methoxide in apolar aprotic solvent such as N,N-dimethylformamide at temperatures fromabout −10° C. to about 30° C. and subsequently heated to 40° C. to about80° C. to provide stilbenes 1-1 (Scheme 2, step a).

Aryl halides 2-3, wherein R¹, R², R³, R⁴, and R⁵ are as previouslydisclosed, may be treated with vinylbenzenes 2-4, wherein R⁶ and R⁹ areas previously disclosed, in the presence of a transition metal catalystsuch as palladium(II) acetate and a bisphosphine ligand such as1,1′-bis(diphenylphosphino)ferrocene in a basic solvent such astriethylamine at temperatures from about 60° C. to about 100° C. toprovide stilbenes 1-1 (Scheme 2, step b). Alternatively, Aryl halides2-3 may be treated with vinylboronates 2-5, wherein R⁶ and R⁹ are aspreviously disclosed, in the presence of a transition metal catalystsuch as tetrakis(triphenylphosphine)palladium(O) and a base such aspotassium carbonate in a solvent mixture such as 1,2-dimethoxyethane andwater at temperatures from about 60° C. to about 100° C. to providestilbenes 1-1 (Scheme 2, step c).

In yet another embodiment, stilbenes 1-1 may also be prepared by theWittig olefination method (Chalal, M.; Vervandier-Fasseur, D.; Meunier,P.; Cattey, H.; Hierso, J.-C. Tetrahedron 2012, 68, 3899-3907) asoutlined in Scheme 2.5. Phenyl carbonyls 2-1, wherein R¹, R², R³, R⁴,and R⁵ are as previously disclosed and R⁶ is H, may be treated withalkoxy benzyl triphenylphosphonium chlorides 2.5-2 in the presence of abase such as n-butyl lithium in a polar aprotic solvent such astetrahydrofuran at temperatures from about −78° C. to ambienttemperature to provide stilbenes 1-1 (Scheme 2.5, step a).

Preparation of Cyclopropyl Amides

Cyclopropyl amides 3-3, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰,R¹¹, R¹², X¹, X², and Q² are as previously disclosed, and X³ is aspreviously disclosed and OH, may be prepared by treatment with amines oramine salts 3-2, wherein R¹⁰, R¹¹, R¹², X¹, X², Q², and X³ are aspreviously disclosed, and activated carboxylic acids 3-1, wherein A isan activating group, and R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are aspreviously disclosed, with a base, such as triethylamine,diisopropylethylamine, 4-methylmorpholine, 4-dimethylaminopyridine, orpyridine in an anhydrous aprotic solvent such as dichloromethane,tetrahydrofuran, 1,2-dichloroethane, dimethylformamide, or anycombination thereof, at temperatures between about 0° C. and about 120°C. (Scheme 3, step a).

Activated carboxylic acids 3-1 may be an acid halide, such as an acidchloride, an acid bromide, or an acid fluoride; a carboxylic ester, suchas a para-nitrophenyl ester, a pentafluorophenyl ester, an ethyl(hydroxyiminio)cyanoacetate ester, a methyl ester, an ethyl ester, abenzyl ester, an N-hydroxysuccinimidyl ester, a hydroxybenzotriazol-1-ylester, or a hydroxypyridyltriazol-1-yl ester; an O-acylisourea; an acidanhydride; or a thioester. Acid chlorides may be prepared from thecorresponding carboxylic acids by treatment with a dehydratingchlorinating reagent, such as oxalyl chloride or thionyl chloride.Activated carboxylic esters 3-1 may be prepared from carboxylic acids insitu with a uronium salt, such as1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxid hexafluorophosphate (HATU),O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate(HBTU), or(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeniumhexafluorophosphate (COMU). Activated carboxylic esters 3-1 may also beprepared from carboxylic acids in situ with a phosphonium salt such asbenzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBop). Activated carboxylic esters 3-1 may also be prepared fromcarboxylic acids in situ with a coupling reagent such as1-(3-dimethylamino propyl)-3-ethylcarbodiimide, propylphosphonicanhydride, or dicyclohexylcarbodiimide with or without the presence of atriazole such as hydroxybenzotriazole.monohydrate (HOBt) or1-hydroxy-7-azabenzotriazole (HOAt). O-Acylisoureas may be prepared witha dehydrating carbodimide such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide. Activatedcarboxylic esters 3-1 may also be prepared from carboxylic acids in situwith a coupling reagent such as 2-chloro-1,3-dimethylimidazolidiniumhexafluorophosphate (CIP) in the presence of a triazole such as1-hydroxy-7-azabenzotriazole (HOAt).

Cyclopropyl amides 3-3 containing a sulfide may be oxidized to thecorresponding sulfoxide or sulfone by treatment with about oneequivalent of meta-chloroperoxybenzoic acid (sulfoxide) in a polaraprotic solvent such as dichloromethane or about two equivalents ofmeta-chloroperoxybenzoic acid (sulfone) at temperatures between about 0°C. to about 40° C. Alternatively, cyclopropyl amides 3-3 containing asulfide may be oxidized to the corresponding sulfoxide or sulfone bytreatment with one equivalent of sodium perborate in a protic solventsuch as acetic acid (sulfoxide) or two equivalents of sodium perborate(sulfone). The oxidation may be performed at temperatures between about40° C. to about 100° C. using about 1.5 equivalents of sodium perborateto provide chromatographically separable mixtures of sulfoxide andsulfone cyclopropyl amides 3-3. Alternatively, cyclopropyl amides 3-3containing a sulfide may be oxidized to the corresponding sulfilimine bytreating with about one equivalent of an amine such as cyanamide, aboutone equivalent of a base such as potassium tert-butoxide, and betweenone and two equivalents of an oxidant such as N-bromosuccinimide in apolar protic solvent such as methanol at temperatures between about 0°C. to about 40° C. The sulfilimine may be further oxidized to thecorresponding sulfoximine by treatment with about one equivalent ofmeta-chloroperoxybenzoic acid and about two equivalents of potassiumcarbonate in a mixture of solvents such as 2:1:1ethanol:dichloromethane:water at temperatures between about 0° C. toabout 40° C.

Cyclopropyl amides 3-3, wherein X¹, X², X⁴, X⁵, X⁶, X⁷, or, X⁸ is N maybe oxidized to the corresponding N-oxide by treatment with about oneequivalent of meta-chloroperoxybenzoic acid in a polar aprotic solventsuch as dichloromethane at temperatures between about 0° C. to about 40°C.

Cyclopropyl amides 3-3, wherein R³ is NO₂ may be reduced to thecorresponding NH₂ by treatment with an acid source, such as ammoniumchloride, and iron in a polar protic solvent, such as methanol, water,or any combination thereof, at temperatures from about 20° C. to about60° C.

Amines or amine salts 3-2, wherein Q² is O may be treated directly witha source of sulfur, such as phosphorus pentasulfide or2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide(Lawesson's reagent) with or without additives such as1,1,1,3,3,3-hexamethyldisoloxane, in an aprotic solvent chosen fromtetrahydrofuran, dichloromethane, chloroform, toluene, or pyridine, attemperatures from about 40° C. to about 120° C. to provide amines oramine salts 3-2, wherein Q² is S.

Cyclopropyl amides 4-3, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹,R¹⁰, R¹¹, R¹², X¹, X², and X³ are as previously disclosed, may beprepared by treatment with amines or amine salts 4-2, wherein X³ is aspreviously disclosed, and activated carboxylic acids 4-1, wherein A isan activating group, and R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹,R^(° 1), R¹¹, R¹², X¹, and X² are as previously disclosed, with a base,such as triethylamine, diisopropylethylamine, 4-methylmorpholine,4-dimethylaminopyridine, or pyridine in an anhydrous aprotic solventsuch as dichloromethane, tetrahydrofuran, 1,2-dichloroethane,dimethylformamide, or any combination thereof, at temperatures betweenabout 0° C. and about 120° C. (Scheme 4, step a).

Activated carboxylic acids 4-1 may be an acid halide, such as an acidchloride, an acid bromide, or an acid fluoride; a carboxylic ester, suchas a p-nitrophenyl ester, a pentafluorophenyl ester, an ethyl(hydroxyimino)cyanoacetate ester, a methyl ester, an ethyl ester, abenzyl ester, an N-hydroxysuccinimidyl ester, a hydroxybenzotriazol-1-ylester, or a hydroxypyridyltriazol-1-yl ester; an O-acylisourea; an acidanhydride; or a thioester. Acid chlorides may be prepared from thecorresponding carboxylic acids by treatment with a dehydratingchlorinating reagent, such as oxalyl chloride or thionyl chloride.Activated carboxylic esters 4-1 may be prepared from carboxylic acids insitu with a uronium salt, such as1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxid hexafluorophosphate (HATU),O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate(HBTU), or(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeniumhexafluorophosphate (COMU). Activated carboxylic esters 4-1 may also beprepared from carboxylic acids in situ with a phosphonium salt such asbenzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBop). Activated carboxylic esters 4-1 may also be prepared fromcarboxylic acids in situ with a coupling reagent such as1-(3-dimethylamino propyl)-3-ethylcarbodiimide, propylphosphonicanhydride, or dicyclohexylcarbodiimide with or without the presence of atriazole such as hydroxybenzotriazole.monohydrate (HOBt) or1-hydroxy-7-azabenzotriazole (HOAt). O-Acylisoureas may be prepared witha dehydrating carbodimide such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide. Activatedcarboxylic esters 4-1 may also be prepared from carboxylic acids in situwith a coupling reagent such as 2-chloro-1,3-dimethylimidazolidiniumhexafluorophosphate (CIP) in the presence of a triazole such as1-hydroxy-7-azabenzotriazole (HOAt).

Cyclopropyl amides 5-2, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹,R¹⁰, R¹¹, R¹², X¹, X², Q², R¹⁵, X⁴, X⁵, X⁶, X⁷, and X⁸ are as previouslydisclosed, may be prepared by treatment of amines 5-1, wherein R¹, R²,R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹, R¹⁰, R¹¹, R¹², X¹, X², Q², R¹⁵, X⁴, X⁵,X⁶, X⁷, and X⁸ are as previously disclosed, with a methylating agentsuch as methylboronic acid and a copper catalyst such as diacetoxycopperin the presence of an aprotic amine base like pyridine in a solvent suchas 1,4-dioxane at a temperature of about 110° C. (Scheme 5, step a).

Cyclopropyl amides 5-4, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹,R¹⁰, R¹¹, R¹², X¹, X², Q², R¹⁵, X⁴, X⁵, X⁶, X⁷, and X⁸ are as previouslydisclosed, and L is (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₃-C₆)cycloalkyl,(C₁-C₆)haloalkyl, (C₁-C₆)alkylphenyl, and (C₁-C₆)alkoxy, wherein eachalkyl, alkenyl, cycloalkyl, haloalkyl, and phenyl, may be optionallysubstituted with one or more substituents selected from F, Cl, Br, I,CN, OH, NH₂, NO₂, oxo, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, andC(O)O(C₁-C₆)alkyl, may be prepared by treatment of amines 5-1, whereinR¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹, R¹⁰, R¹, R¹², X¹, X², Q², R¹⁵,X⁴, X⁵, X⁶, X⁷, and X⁸ are as previously disclosed, or amines 5-2,wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹, R¹⁰, R¹¹, R¹², X¹, X²,Q², R¹⁵, X⁴, X⁵, X⁶, X⁷, and X⁸ are as previously disclosed, andactivated carboxylic acids 5-3, wherein A is an activating group, and Lis as previously disclosed, with a base, such as triethylamine,diisopropylethylamine, 4-methylmorpholine, 4-dimethylaminopyridine, orpyridine, in an anhydrous aprotic solvent such as dichloromethane,tetrahydrofuran, 1,2-dichloroethane, N,N-dimethylformamide, or anycombination thereof, at temperatures between about 0° C. and about 120°C. (Scheme 5, steps b and c).

Activated carboxylic acids 5-3 may be an acid halide, such as an acidchloride, an acid bromide, or an acid fluoride; a carboxylic ester, suchas a p-nitrophenyl ester, a pentafluorophenyl ester, an ethyl(hydroxyiminio)cyanoacetate ester, a methyl ester, an ethyl ester, abenzyl ester, an N-hydroxysuccinimidyl ester, a hydroxybenzotriazol-1-ylester, or a hydroxypyridyltriazol-1-yl ester; an O-acylisourea; an acidanhydride; or a thioester. Acid chlorides may be prepared from thecorresponding carboxylic acids by treatment with a dehydratingchlorinating reagent, such as oxalyl chloride or thionyl chloride.Activated carboxylic esters 5-3 may be prepared from carboxylic acids insitu with a uronium salt, such as1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxid hexafluorophosphate (HATU),O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate(HBTU), or(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeniumhexafluorophosphate (COMU). Activated carboxylic esters 5-3 may also beprepared from carboxylic acids in situ with a phosphonium salt such asbenzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBop). Activated carboxylic esters 5-3 may also be prepared fromcarboxylic acids in situ with a coupling reagent, such as1-(3-dimethylamino propyl)-3-ethylcarbodiimide ordicyclohexylcarbodiimide, in the presence of a triazole such ashydroxybenzotriazole.monohydrate (HOBt) or 1-hydroxy-7-azabenzotriazole(HOAt). O-Acylisoureas may be prepared with a dehydrating carbodimidesuch as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide ordicyclohexylcarbodiimide. Activated carboxylic esters 5-3 may also beprepared from carboxylic acids in situ with a coupling reagent such as2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) in thepresence of a triazolol such as 1-hydroxy-7-azabenzotriazole (HOAt).Activated carboxylic esters 5-3 may also be prepared from carboxylicacids in situ with a coupling reagent such as2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (T3P®)in the presence of a base such as pyridine.

Cyclopropyl amides 6-3, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹,R¹⁰, R¹¹, R¹², X¹, X², Q², R¹⁵, X⁵, X⁶, X⁷, and X⁸ are as previouslydisclosed, may be prepared by treatment of aldehydes or ketones 6-1wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹, R¹⁰, R¹¹, R¹², X¹, X²,Q², R¹⁵, X⁵, X⁶, X⁷, and X⁸ are as previously disclosed, andhydroxylamines 6-2, wherein each alkyl may be optionally substitutedwith one or more substituents selected from F, Cl, Br, I, CN, OH, NH₂,NO₂, oxo, (C₁-C₅)alkyl, (C₁-C₅)alkoxy, and C(O)O(C₁-C₅)alkyl, with orwithout an acid, such as acetic acid, in a polar aprotic solvent such asethanol, at temperatures between about 0° C. and about 80° C. (Scheme 6,step a).

Cyclopropyl amides 7-3, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹,R¹⁰, R¹¹, R¹², X¹, X², Q², R¹⁵, X⁴, X⁵, X⁷, and X⁸ are as previouslydisclosed, may be prepared by treatment of aldehydes or ketones 7-1wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹, R¹⁰, R¹¹, R¹², X¹, X²,Q², R¹⁵, X⁴, X⁵, X⁷, and X⁸ are as previously disclosed, andhydroxylamines 7-2, wherein each alkyl may be optionally substitutedwith one or more substituents selected from F, Cl, Br, I, CN, OH, NH₂,NO₂, oxo, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, and C(O)O(C₁-C₆)alkyl, with orwithout an acid, such as acetic acid, in a polar aprotic solvent such asethanol, at temperatures between about 0° C. and about 80° C. (Scheme 7,step a).

Cyclopropyl amides 8-3, wherein R¹, R², R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹, R¹⁰,R¹¹, R¹², X¹, X², X³, and Q² are as previously disclosed, may beprepared by treatment of aryl bromide 8-1, wherein R¹, R², R⁴, R⁵, R⁶,R⁷, R⁸, R⁹, Q¹, R¹⁰, R¹¹, R¹², X¹, X², X³, and Q² are as previouslydisclosed, and (C₁-C₆)alkenyl or (C₁-C₆)alkynyl stannane 8-2, whereineach alkenyl or alkynyl group may be optionally substituted with one ormore substituents selected from F and SiMe₃, with a palladium source,such as bis(triphenylphosphine)palladium(II) dichloride in an aproticsolvent such as 1,4-dioxane, at temperatures between about 20° C. andabout 120° C. (Scheme 8, step a).

Cyclopropyl amides 8-3, wherein (C₁-C₆)alkynyl is trimethylsilyl alkynemay be treated with a source of fluoride, such as potassium fluoride, ina polar solvent, such as dichloromethane, methanol, or a combinationthereof, at temperatures from about 0° C. to about 50° C. to providecyclopropyl amide 8-3, wherein (C₁-C₆)alkynyl is CCH.

Cyclopropyl amides 9-3, wherein R¹, R², R³, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹, R¹⁰,R¹¹, R¹², X¹, X², X³, and Q² are as previously disclosed, may beprepared by treatment of aryl bromide 9-1, wherein R¹, R², R³, R⁵, R⁶,R⁷, R⁸, R⁹, Q¹, R¹⁰, R¹¹, R¹², X¹, X², X³, and Q² are as previouslydisclosed, and (C₁-C₆)alkenyl or (C₁-C₆)alkynyl stannane 9-2, whereineach alkenyl or alkynyl group may be optionally substituted with one ormore substituents selected from F and SiMe₃, with a palladium source,such as bis(triphenylphosphine)palladium(II) dichloride in an aproticsolvent such as 1,4-dioxane, at temperatures between about 20° C. andabout 120° C. (Scheme 9, step a).

Cyclopropyl amides 9-3, wherein (C₁-C₆)alkynyl is trimethylsilyl alkynemay be treated with a source of fluoride, such as potassium fluoride, ina polar solvent, such as dichloromethane, methanol, or a combinationthereof, at temperatures from about 0° C. to about 50° C. to providecyclopropyl amide 9-3, wherein (C₁-C₆)alkynyl is CCH.

Cyclopropyl amides 10-3, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R, R⁹, Q¹,R¹⁰, R¹¹, R¹², X¹, X², X⁴, X⁵, X⁶, X⁷, and X⁸ are as previouslydisclosed, may be prepared by treatment of primary amides 10-1, whereinR¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹, R¹⁰, R¹¹, R¹², X¹, and X² are aspreviously disclosed, and aryl bromides 10-2, wherein X⁴, X⁵, X⁶, X⁷,and X⁸ are as previously disclosed, with a palladium catalyst such astris(dibenzylideneacetone)dipalladium(O), a phosphine ligand such as4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene, and an inorganic basesuch as cesium carbonate, in an aprotic solvent such as 1,4-dioxane, attemperatures between about 60° C. and about 80° C. (Scheme 10, step a).

Cyclopropyl amides 11-3, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹,R¹⁰, R¹¹, R¹², X¹, X², X⁴, X⁵, X⁶, X⁷, and X⁸ are as previouslydisclosed, may be prepared by treatment of 11-1, wherein R¹, R², R³, R⁴,R⁵, R⁶, R⁷, R⁸, R⁹, Q¹, R¹⁰, R¹¹, R¹², X¹, X², X⁴, X⁵, X⁶, X⁷, and X⁸are as previously disclosed, with a metal such as palladium on carbon inthe presence of a reducing agent such as hydrogen gas in a solvent suchas ethyl acetate or with a metal such as iron in the presence of areducing agent such as ammonium chloride in a solvent mixture such asmethanol and water at a temperature of about 25° C. to about 60° C.(Scheme 11, step a). Alternatively, cyclopropyl amides 11-3, wherein R¹,R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹, R¹⁰, R¹¹, R¹², X¹, X², X⁴, X⁵, X⁶,X⁷, and X⁸ are as previously disclosed, may be prepared by treatment of11-2 wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹, R¹⁰, R¹¹, R¹², X¹,X², X⁴, X⁵, X⁶, X⁷, and X⁸ are as previously disclosed, with ananhydrous acid solution such as hydrochloric acid in 1,4-dioxane anddichloromethane at a temperature of about 25° C. (Scheme 11, step b).

Cyclopropyl amides 12-3, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, Q¹,R¹⁰, R¹¹, R¹², X¹, X², Q², R¹⁵, X⁴, X⁵, X⁶, X⁷, and X⁸ are as previouslydisclosed and L² is a (C₁-C₆)alkenyl or (C₁-C₆)alkynyl group, whereineach alkenyl or alkynyl group may be optionally substituted with one ormore substituents selected from F, Cl, and (C₁-C₆)alkyl, may be preparedby treatment of aryl halides 12-1, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁸, R⁹, Q¹, R¹⁰, R¹¹, R¹², X¹, X², Q², R¹⁵, X⁴, X⁵, X⁶, X⁷, and X⁸ areas previously disclosed, with a stannane such as 12-2, wherein L² is aspreviously disclosed, in the presence of a metal catalyst such asbis(triphenylphosphine)palladium(II) dichloride in an aprotic solventlike 1,4-dioxane at a temperature of about 90° C. (Scheme 12, step a).

In some embodiments, 1-3 may be prepared from the α,β-unsaturatedaldehyde 13-1, wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁹ are as previously.It will be understood by one skilled in the art that compound 13-1 maybe synthesized via Aldol condensation (see Yoshikawa, M.; Kamei, T. PCTInt. Appl. 2010123006, 2010) of an appropriately substituted,commercially available aldehyde and acetaldehyde. Treatment of 13-1 witha (C₁-C₆)alkyl orthoformate, in the presence of an acid whose pH is 0-5such as hydrobromic acid, N-bromosuccinimide, hydrochloric acid,N-chlorosuccinimide, and pyridinium p-toluenesulfonate (PPTS), in a(C₁-C₆)alkanol solvent, at a temperature from 0° C. to ambient and underambient pressure provides the acetal 13-2, wherein R¹, R², R³, R⁴, R⁵,R⁶, and R⁹ are as previously disclosed and R^(a) is a (C₁-C₆)alkyl orR^(a) and R^(a) taken together can form a cyclic acetal (Scheme 13, stepa). The acetal 13-2 may be converted to the cyclopropyl acetal 13-3,wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, and R^(a) are as previouslydisclosed, by treatment with a carbene source such as a haloform, forexample, bromoform or chloroform, in the presence of an inorganic base,such as sodium or potassium hydroxide or sodium or potassium carbonate,and a phase-transfer catalyst such as benzyl triethylammonium chloride,(−)-N-dodecyl-N-methylephedrinium bromide, tetramethylammonium bromide,tetrapropylammonium bromide, tetrabutylammonium tetrafluoroborate,tetramethylammonium chloride or tetrabutylammonium hexafluorophosphateat a temperature from about ambient temperature up to below the boilingpoint of the haloform (Scheme 13, step b). Caution: Step B is anexothermic reaction and careful control of the exotherm should beexercised when conducting this reaction. The cyclopropyl acetal 13-3 maybe transformed into the aldehyde 13-4, wherein R¹, R², R³, R⁴, R⁵, R⁶,R⁷, R⁸, and R⁹ are as previously disclosed, in a polar solvent selectedfrom the group consisting of acetone, acetonitrile, methanol, ethanol,nitromethane, N,N-dimethylformamide, dimethyl sulfoxide, ethyl acetate,tetrahydrofuran and 1,4-dioxane, in the presence of an aqueous mineralacid selected from the group consisting of nitric acid, hydrochloricacid, hydrobromic acid, and sulfuric acid (Scheme 5, step c) at ambienttemperature. The cyclopropyl acid 1-3, wherein R¹, R², R³, R⁴, R⁵, R⁶,R⁷, R⁸, and R⁹ are as previously disclosed, may be obtained by oxidationof the aldehyde 13-4 with oxidants such sodium permanganate or potassiumpermanganate, or under Pinnick oxidation conditions in a polar aproticsolvent selected from the group consisting of acetone, acetonitrile,N,N-dimethylformamide, dimethyl sulfoxide, ethyl acetate,tetrahydrofuran and 1,4-dioxane at a temperature from about 0° C. toabout ambient temperature (Scheme 13, step d). Standard safetyprecautions should be exercised because an exotherm may occur whenconducting this reaction.

It will be understood by those skilled in the art that, in someembodiments, the cyclopropyl acid 1-3, wherein R¹, R², R³, R⁴, R⁵, R⁶,R⁷, R⁸, and R⁹ are as previously disclosed, may be resolved into its(R,R) and (S,S) enantiomers via a method such as that in Kovalenko V.N., Kulinkovich O. G. Tetrahedron: Asymmetry 2011, 22, 26 (Scheme 14,step a).

EXAMPLES

These examples are for illustration purposes and are not to be construedas limiting this disclosure to only the embodiments disclosed in theseexamples.

Starting materials, reagents, and solvents that were obtained fromcommercial sources were used without further purification. Anhydroussolvents were purchased as Sure/Seal™ from Aldrich and were used asreceived. Melting points were obtained on a Thomas Hoover Unimeltcapillary melting point apparatus or an OptiMelt Automated Melting PointSystem from Stanford Research Systems and are uncorrected. Examplesusing “room temperature” were conducted in climate controlledlaboratories with temperatures ranging from about 20° C. to about 24° C.Molecules are given their known names, named according to namingprograms within ISIS Draw, ChemDraw, or ACD Name Pro. If such programsare unable to name a molecule, such molecule is named using conventionalnaming rules. ¹H NMR spectral data are in ppm (δ) and were recorded at300, 400, 500, or 600 MHz; ¹³C NMR spectral data are in ppm (δ) and wererecorded at 75, 100, or 150 MHz, and ¹⁹F NMR spectral data are in ppm(δ) and were recorded at 376 MHz, unless otherwise stated.

Example 1: Preparation oftrans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxylic acid(C1)

Ruthenium(III) chloride (0.080 g, 0.39 mmol) was added to a stirredmixture oftrans-1,3-dichloro-5-(−2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene(C22) (2.8 g, 7.7 mmol) and sodium periodate (33 g, 160 mmol) inwater:ethyl acetate:acetonitrile (8:1:1, 155 mL) at 23° C. The resultingbiphasic brown mixture was vigorously stirred at 23° C. for 5 hours. Thereaction mixture was diluted with water (1000 mL) and extracted withdichloromethane (4×200 mL). The combined organic layers were dried overmagnesium sulfate, filtered, and concentrated. The residue was dilutedwith a sodium hydroxide solution (1 M, 100 mL) and washed with diethylether (4×50 mL). The aqueous layer was adjusted to pH 2, usingconcentrated hydrochloric acid, and extracted with dichloromethane (3×50mL). The combined organic layers were dried over magnesium sulfate,filtered, and concentrated to afford the title product as a light brownpowder (0.78 g, 34%): mp 117-120° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 13.38(br s, 1H), 7.52-7.65 (m, 3H), 3.57 (d, J=8.5 Hz, 1H), 3.50 (d, J=8.5Hz, 1H); IR (thin film) 3083 (s), 3011 (s), 1731 (s), 1590 (w), 1566(s), 1448 (w), 1431 (m), 1416 (m) cm⁻¹.

The following compounds were prepared in like manner to the procedureoutlined in Example 1:

trans-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropanecarboxylic acid(C2)

Isolated as a yellow powder (1.5 g, 39%): ¹H NMR (400 MHz, CDCl₃) δ 7.31(d, J=0.7 Hz, 2H), 3.40 (d, J=8.2 Hz, 1H), 2.86 (d, J=8.3 Hz, 1H); ¹³CNMR (101 MHz, CDCl₃) δ 171.05, 134.55, 132.44, 131.75, 128.89, 61.18,39.26, 37.14; ESIMS m/z 333 ([M−H]⁻).

trans-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropanecarboxylic acid(C3)

Isolated as a pale yellow solid (3.2 g, 51%): ¹H NMR (400 MHz, CDCl₃) δ7.47 (d, J=8.3 Hz, 1H), 7.37 (d, J=1.6 Hz, 1H), 7.12 (ddd, J=8.3, 2.1,0.6 Hz, 1H), 3.43 (d, J=8.3 Hz, 1H), 2.86 (d, J=8.3 Hz, 1H); ¹³C NMR(101 MHz, CDCl₃) δ 171.52, 132.91, 132.76, 132.29, 130.66, 130.62,128.02, 61.48, 39.65, 37.13; ESIMS m/z 298 ([M−H]⁻).

Example 2: Preparation oftrans-2,2-dichloro-3-(4-(trifluoromethyl)phenyl)cyclopropanecarboxylicacid (C4)

To a stirred mixture oftrans-1-(2,2-dichloro-3-(4-(trifluoromethyl)phenyl)cyclopropyl)-4-methoxybenzene(C25) (3.50 g, 9.60 mmol) and sodium periodate (30.8 g, 144 mmol) inwater:ethyl acetate:acetonitrile (8:1:1, 200 mL) was addedruthenium(III) chloride (0.100 g, 0.400 mmol) at 23° C. The resultingmixture was vigorously stirred at 23° C. for about 5 hours. The reactionmixture was diluted with dichloromethane and washed with water. Thecombined organic layers were dried over sodium sulfate, filtered, andconcentrated. Purification by flash column chromatography provided thetitle compound as an off-white solid (0.630 g, 38%): mp 100-102° C.; ¹HNMR (400 MHz, DMSO-d₆) δ 13.43 (brs, 1H), 7.77-7.73 (m, 2H), 7.67-7.64(m, 2H), 3.55 (d, J=8.8 Hz, 1H), 3.44 (d, J=8.8 Hz, 1H); ESIMS m/z 347([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 2:

trans-2,2-Dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane carboxylicacid (C5)

Isolated as an off-white solid (0.81 g, 33%): mp 86-88° C.; ¹H NMR (400MHz, DMSO-d₆) δ 13.37 (brs, 1H), 7.83 (s, 1H), 7.76-7.69 (m, 2H),7.65-7.59 (m, 1H), 3.59-3.51 (m, 2H); ESIMS m/z 297 ([M−H]⁻).

trans-2,2-Dichloro-3-(3-chloro-4-(trifluoromethoxy)phenyl)cyclopropanecarboxylicacid (C6)

Isolated as an off-white solid (0.3 g, 19%): mp 134-136° C.; ¹H NMR (400MHz, DMSO-d₆) δ 13.45 (brs, 1H), 7.82 (d, J=1.6 Hz, 1H), 7.60-7.53 (m,2H), 3.53-3.47 (m, 2H); ESIMS m/z 347 ([M−H]⁻).

trans-2,2-Dichloro-3-(2,4,5-trichlorophenyl)cyclopropanecarboxylic acid(C7)

Isolated as an off-white solid (0.267 g, 18%): mp 189-192° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 13.44 (brs, 1H), 8.01 (s, 1H), 7.82 (s, 1H), 3.52(d, J=8.2 Hz, 1H), 3.29 (d, J=8.2 Hz, 1H); ESIMS m/z 333 ([M−H]⁻).

trans-3-(3,5-bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropanecarboxylicacid (C8)

Isolated as an off-white solid (0.5 g, 31%): mp 112-114° C.; ¹H NMR (400MHz, DMSO-d₆) δ 13.43 (brs, 1H), 8.22 (s, 2H), 8.08 (s, 1H), 3.80-3.71(m, 2H); ESIMS m/z 365 ([M−H]⁻).

trans-2,2-dichloro-3-(3,5-dibromophenyl)cyclopropanecarboxylic acid (C9)

Isolated as an off-white solid (0.5 g, 24%): mp 157-159° C.; ¹H NMR (400MHz, DMSO-d₆) δ 13.36 (brs, 1H), 7.81 (d, J=1.5 Hz, 2H), 7.72 (d, J=1.5Hz, 2H), 3.57-3.53 (m, 1H), 3.51-3.47 (m, 1H); ESIMS m/z 387 ([M−H]⁻).

trans-2,2-Dichloro-3-(3-chloro-5-(trifluoromethyl)phenyl)cyclopropanecarboxylicacid (C10)

Isolated as an off-white solid (0.73 g, 28%): mp 113-115° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 13.39 (brs, 1H), 7.91 (s, 1H), 7.86 (s, 1H), 7.84(s, 1H), 3.69-3.60 (m, 2H); ESIMS m/z 333 ([M−H]⁻).

trans-2,2-Dichloro-3-(3,5-dichloro-4-fluorophenyl)cyclopropanecarboxylicacid (C11)

Isolated as an off-white solid (0.539 g, 34%): ¹H NMR (400 MHz,DMSO-d₆): δ 13.37 (brs, 1H), 7.71 (d, J=6.4 Hz, 2H), 3.42 (s, 2H); ESIMSm/z 317 ([M−H]⁻).

trans-3-(4-Bromo-3,5-dichlorophenyl)-2,2-dichlorocyclopropanecarboxylicacid (C12)

Isolated as an off-white solid (0.100 g, 10%): ¹H NMR (400 MHz, DMSO-d₆)δ 13.37 (brs, 1H), 7.76 (s, 3H), 3.57 (d, J=8.8 Hz, 1H), 3.48 (d, J=8.8Hz, 1H); ESIMS m/z 377 ([M−H]⁻).

trans-3-(3-Bromo-5-chlorophenyl)-2,2-dichlorocyclopropanecarboxylic acid(C13)

Isolated as an off-white solid (0.4 g, 25%): mp 161-163° C.; ¹H NMR (400MHz, DMSO-d₆) δ 13.38 (br s, 1H), 7.70 (d, J=5.3 Hz, 2H), 7.66-7.52 (m,1H), 3.59-3.43 (m, 2H); ESIMS m/z 341 ([M−H]⁻).

trans-2,2-Dichloro-3-(3-chloro-5-fluorophenyl)cyclopropanecarboxylicacid (C14)

Isolated as an off-white solid (0.700 g, 25%): mp 138-140° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 13.38 (brs, 1H), 7.46 (s, 1H), 7.42 (td, J=2.0, 8.7Hz, 1H), 7.37 (d, J=9.8 Hz, 1H), 3.52 (q, J=8.5 Hz, 2H); ESIMS m/z 281([M−H]⁻).

trans-2,2-Dichloro-3-(4-chloro-3-fluorophenyl)cyclopropanecarboxylicacid (C15)

Isolated as an off-white solid (0.500 g, 20%): mp 140-142° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 13.40 (brs, 1H), 7.59 (m, 1H), 7.55 (d, J=8.4 Hz,1H), 7.33 (dd, J=2.0, 8.4 Hz, 1H), 3.55-3.38 (m, 2H); ESIMS m/z 281([M−H]⁻).

trans-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarboxylicacid (C16)

Isolated as an off-white solid (1.0 g, 53%): mp 121-123° C.; ¹H NMR (400MHz, DMSO-d₆) δ 13.35 (brs, 1H), 7.71 (dd, J=2.0, 7.2 Hz, 1H), 7.53-7.35(m, 2H), 3.50-3.41 (m, 2H); ESIMS m/z 281 ([M−H]⁻).

trans-2,2-Dichloro-3-(3-chloro-5-methylphenyl)cyclopropanecarboxylicacid (C17)

Isolated as an off-white solid (1.0 g, 42%): mp 124-126° C.; ¹H NMR (400MHz, DMSO-d₆) δ 13.33 (brs, 1H), 7.30 (s, 1H), 7.23 (s, 1H), 7.21 (s,1H), 3.38 (s, 2H), 2.31 (s, 3H); ESIMS m/z 277 ([M−H]⁻).

trans-2,2-Dichloro-3-(3,5-dichloro-4-methylphenyl)cyclopropanecarboxylicacid (C18)

Isolated as an off-white solid (0.8 g, 40%): mp 181-183° C.; ¹H NMR (400MHz, DMSO-d₆) δ 13.40 (s, 1H), 7.56 (s, 2H), 3.53-3.50 (m, 1H),3.46-3.43 (m, 1H), 2.40 (s, 3H); ESIMS m/z 311 ([M−H]⁻).

trans-2,2-Dichloro-3-(3,4-dichloro-5-methylphenyl)cyclopropanecarboxylicacid (C19)

Isolated as an off-white solid (0.73 g, 45%): mp 157-159° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 13.40 (s, 1H), 7.59 (d, J=2.0 Hz, 1H), 7.44 (d,J=1.6 Hz, 1H), 3.43 (q, J=8.5 Hz, 2H), 2.39 (s, 3H); ESIMS m/z 311([M−H]⁻).

trans-2,2-Dichloro-3-(4-(perfluoroethyl)phenyl)cyclopropanecarboxylicacid (C20)

Isolated as an off-white solid (0.020 g, 10%): mp 116-118° C.; ¹H NMR(300 MHz, CDCl₃) δ 7.63 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 3.53(d, J=8.4 Hz, 1H), 2.94 (d, J=8.4 Hz, 1H); ESIMS m/z 347 ([M−H]⁻).

trans-2,2-dichloro-3-(4-ethoxyphenyl)cyclopropanecarboxylic acid (C21)

Isolated as an off-white solid (0.025 g, 5%): mp 129-130° C.; ¹H NMR(400 MHz, CDCl₃) δ 7.16 (d, J=8.4 Hz, 2H), 6.88 (d, J=8.31 Hz, 2H), 4.03(q, J=6.8 Hz, 2H), 3.41 (d, J=8.0 Hz, 1H), 2.81 (d, J=8.0 Hz, 1H), 1.41(t, J=6.8 Hz, 3H); ESIMS m/z 273 ([M−H]⁻).

Example 3: Preparation oftrans-1,3-dichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene(C22)

Aqueous sodium hydroxide (50%, 6.8 mL, 130 mmol) was added to a stirredsolution of (E)-1,3-dichloro-5-(4-methoxystyryl)benzene (C43) (2.4 g,8.6 mmol) and N-benzyl-N,N-diethylethanaminium chloride (0.20 g, 0.86mmol) in chloroform (14 mL, 170 mmol) at 23° C. The resulting biphasic,dark brown mixture was vigorously stirred at 23° C. for 24 hours. Thereaction mixture was diluted with water (200 mL) and extracted withdichloromethane (2×100 mL). The combined organic layers were dried overmagnesium sulfate, filtered, and concentrated to afford the titleproduct as a brown oil (2.8 g, 90%): ¹H NMR (400 MHz, CDCl₃) δ 7.34 (t,J=1.8 Hz, 1H), 7.21-7.30 (m, 4H), 6.93 (m, 2H), 3.83 (s, 3H), 3.14 (d,J=8.5 Hz, 1H), 3.08 (d, J=8.5 Hz, 1H); IR (thin film) 3075 (w), 2934(w), 2836 (w), 1724 (w), 1640 (w), 1609 (m), 1584 (m), 1568 (s), 1513(s) cm⁻¹.

The following compounds were prepared in like manner to the procedureoutlined in Example 3:

trans-1,2,3-Trichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene(C23)

Isolated as a dark foam (4.7 g, 100%): ¹H NMR (400 MHz, CDCl₃) δ 7.40(d, J=0.6 Hz, 2H), 7.29-7.22 (m, 2H), 6.96-6.89 (m, 2H), 3.83 (s, 3H),3.12 (d, J=8.8 Hz, 1H), 3.06 (d, J=8.7 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃)δ 159.46, 135.08, 134.23, 130.91, 129.85, 129.16, 125.42, 114.02, 64.67,55.32, 39.62, 38.48.

trans-1,2-Dichloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene(C24)

Isolated as an orange-red oil (7.6 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ7.47 (d, J=4.9 Hz, 1H), 7.45 (bs, 1H), 7.30-7.23 (m, 2H), 7.21 (dd,J=8.2, 1.9 Hz, 1H), 6.96-6.90 (m, 2H), 3.83 (s, 3H), 3.11 (app. q, J=8.8Hz, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 159.39, 134.90, 132.62, 131.99,130.90, 130.40, 129.90, 128.33, 125.81, 113.98, 64.94, 55.33, 39.52,38.75.

Example 4: Preparation oftrans-1-(2,2-dichloro-3-(4-(trifluoromethyl)phenyl)cyclopropyl)-4-methoxybenzene(C25)

To a stirred solution of(E)-1-methoxy-4-(4-(trifluoromethyl)styryl)benzene (C46) (4.00 g, 14.0mmol) and N-benzyl-N,N-diethylethanaminium chloride (0.320 g, 14.0 mmol)in chloroform (23.1 g, 288 mmol), was added aqueous sodium hydroxide(50%, 8.64 g, 216 mmol) in water (17 mL) at 23° C., and the resultingmixture was vigorously stirred at 23° C. for 16 hours. The reactionmixture was diluted with water and extracted with dichloromethane. Thecombined organic layers were dried over sodium sulfate, filtered, andconcentrated. Purification by flash column chromatography provided thetitle compound as an off-white solid (3.70 g, 68%): ¹H NMR (300 MHz,CDCl₃) δ 7.65 (d, J=8.4 Hz, 2H), 7.49 (d, J=8.4 Hz, 2H), 7.29 (d, J=8.4Hz, 2H), 6.94 (d, J=8.4 Hz, 2H), 3.83 (s, 3H), 3.19 (s, 2H); ESIMS m/z361 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 4:

trans-1-(2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)-3-(trifluoromethyl)benzene(C26)

Isolated as a brown liquid (3.5 g, 67%): ¹H NMR (300 MHz, CDCl₃) δ7.62-7.50 (m, 4H), 7.29 (d, J=9.0 Hz, 2H), 6.94 (d, J=9.0 Hz, 2H),7.35-7.25 (m, 3H), 7.97-6.88 (m, 1H), 3.83 (s, 3H), 3.19 (m, 2H); ESIMSm/z 361 ([M+H]⁺).

trans-2-Chloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-1-(trifluoromethoxy)benzene(C27)

Isolated as an off-white solid (2.5 g, 65%): ¹H NMR (400 MHz, CDCl₃) δ7.57 (d, J=2.0 Hz, 1H), 7.44 (d, J=8.8 Hz, 1H), 7.35-7.25 (m, 3H),7.97-6.88 (m, 1H), 3.84 (s, 3H), 3.15-3.05 (m, 2H); ESIMS m/z 411([M+H]⁺).

trans-1,2,4-Trichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene(C28)

Isolated as a brown liquid (2.0 g, 58%): EIMS m/z 394 ([M]⁺).

trans-1-(2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene(C29)

Isolated as a brown liquid (3.0 g, 61%): EIMS m/z 428 ([M]⁺).

trans-1,3-Dibromo-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene(C30)

Isolated as a brown liquid (3.0 g, 57%): ¹H NMR (300 MHz, CDCl₃) δ 7.64(s, 1H), 7.45 (s, 2H), 7.25 (d, J=9.0 Hz, 2H), 6.92 (d, J=9.0 Hz, 1H),3.83 (s, 3H), 3.15-3.05 (m, 2H); ESIMS m/z 453 ([M+H]⁺).

trans-1-Chloro-3-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-5-(trifluoromethyl)benzene(C31)

Isolated as a brown solid (4.0 g, 74%): ¹H NMR (300 MHz, CDCl₃) δ 7.64(s, 1H), 7.45 (s, 1H), 7.42 (s, 1H), 7.26 (d, J=9.0 Hz, 2H), 6.93 (d,J=9.0 Hz, 1H), 3.83 (s, 3H), 3.15-3.05 (m, 2H); ESIMS m/z 395 ([M+H]⁺).

trans-1,3-Dichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-2-fluorobenzene(C32)

Isolated as a brown solid (1.6 g, 54%): ¹H NMR (300 MHz, CDCl₃) δ 7.32(d, J=6.0 Hz, 2H), 7.30 (d, J=9.0 Hz, 1H), 6.93 (d, J=9.0 Hz, 1H), 3.83(s, 3H), 3.12-3.05 (m, 2H); ESIMS m/z 297 ([M+H]⁺).

trans-2-Bromo-1,3-dichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cycloropyl)benzene(C33)

Isolated as an off-white solid (1.5 g, 44%): ¹H NMR (300 MHz, CDCl₃) δ7.36 (d, J=9.0 Hz, 2H), 7.20 (s, 2H), 6.93 (d, J=9.0 Hz, 2H), 3.83 (s,3H), 3.15-3.05 (m, 2H); ESIMS m/z 439 ([M+H]⁺).

trans-1-Bromo-3-chloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene(C34)

Isolated as an off-white solid (2.5 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ7.49 (s, 1H), 7.30 (s, 1H), 7.28-7.24 (m, 3H), 6.92 (d, J=8.0 Hz, 2H),3.92 (s, 3H), 3.01 (q, J=8.8 Hz, 2H); ESIMS m/z 405 ([M+H]⁺).

trans-1-Chloro-3-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-5-fluorobenzene(C35)

Isolated as a brown liquid (3.5 g, 67%): ESIMS m/z 345 ([M+H]⁺).

trans-1-Chloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-2-fluorobenzene(C36)

Isolated as an off-white solid (2.5 g, 65%): ESIMS m/z 345 ([M+H]⁺).

trans-2-Chloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-1-fluorobenzene(C37)

Isolated as a brown liquid (2.0 g, 58%): ESIMS m/z 345 ([M+H]⁺).

trans-1-Chloro-3-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-5-methylbenzene(C38)

Isolated as an off-white solid (3.0 g, 47%): ¹H NMR (400 MHz, CDCl₃) δ7.27 (d, J=8.8 Hz, 2H), 7.14 (s, 2H), 7.06 (s, 1H), 6.92 (d, J=8.8 Hz,2H), 3.82 (s, 3H), 3.10 (q, J=8.8 Hz, 2H), 2.36 (s, 3H); ESIMS m/z 341([M+H]⁺).

trans-1,3-Dichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-2-methylbenzene(C39)

Isolated as a brown liquid (2.5 g, 80%): ¹H NMR (400 MHz, CDCl₃) δ 7.25(d, J=8.0 Hz, 2H), 7.17 (d, J=8.8 Hz, 1H), 6.92 (d, J=8.0 Hz, 2H), 6.88(d, J=8.8 Hz, 1H), 3.82 (s, 3H), 3.12-3.03 (m, 2H), 2.47 (s, 3H); ESIMSm/z 375 ([M+H]⁺).

trans-1,2-Dichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-3-methylbenzene(C40)

Isolated as a Brown liquid (4.0 g, 90%): ESIMS m/z 375 ([M+H]⁺).

trans-1-(2,2-Dichloro-3-(4-(perfluoroethyl)phenyl)cyclopropyl)-4-methoxybenzene(C41)

Isolated as an off-white solid (0.5 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ7.60-7.50 (m, 4H), 7.47 (d, J=8.0 Hz, 2H), 6.92 (d, J=8.0 Hz, 2H), 3.82(s, 3H), 3.20 (s, 2H); ESIMS m/z 411 ([M+H]⁺).

trans-4,4′-(3,3-Dichlorocyclopropane-1,2-diyl)bis(ethoxybenzene) (C42)

Isolated as an off-white solid (1.5 g, 45%): ¹H NMR (400 MHz, CDCl₃) δ7.27 (d, J=8.0 Hz, 4H), 6.90 (d, J=8.0 Hz, 4H), 4.04 (q, J=6.8 Hz, 4H),3.09 (s, 2H), 1.42 (t, J=6.8 Hz, 6H); ESIMS m/z 351 ([M+H]⁺).

Example 5: Preparation of (E)-1,3-dichloro-5-(4-methoxystyryl)benzene(C43)

Sodium methoxide powder (98%, 0.63 g, 11 mmol) was added to a stirredsolution of 3,5-dichlorobenzaldehyde (2.0 g, 11 mmol) and diethyl4-methoxybenzylphosphonate (2.0 mL, 11 mmol) in dryN,N-dimethylformamide (38 mL) at 23° C. The resulting heterogeneous darkblue mixture was heated to 80° C., resulting in a dark brown mixture,and stirred for 24 hours. The cooled reaction mixture was diluted withwater (500 mL) and extracted with diethyl ether (3×100 mL). The combinedorganic layers were diluted with hexane (150 mL) and washed with water(300 mL). The organic layer was dried over magnesium sulfate, filtered,and concentrated to afford the title product as a light brown oil (2.4g, 75%): ¹H NMR (400 MHz, CDCl₃) δ 7.44 (m, 2H), 7.34 (d, J=2 Hz, 2H),7.20 (t, J=2 Hz, 1H), 7.06 (d, J=16.5 Hz, 1H), 6.91 (m, 2H), 6.82 (d,J=16.5 Hz, 1H), 3.84 (s, 3H); IR (thin film) 2934 (w), 2835 (w), 1724(w), 1637 (w), 1605 (m), 1581 (m), 1558 (m), 1511 (s) cm⁻¹.

The following compounds were prepared in like manner to the procedureoutlined in Example 5:

(E)-1,2,3-Trichloro-5-(4-methoxystyryl)benzene (C44)

Isolated as an off-white solid (3.7 g, 31%): ¹H NMR (400 MHz, CDCl₃) δ7.49-7.46 (m, 2H), 7.47-7.39 (m, 2H), 7.04 (d, J=16.3 Hz, 1H), 6.93-6.89(m, 2H), 6.78 (d, J=16.3 Hz, 1H), 3.84 (s, 3H); ¹³C NMR (101 MHz, CDCl₃)δ 159.46, 135.08, 134.23, 130.91, 129.85, 129.16, 125.42, 114.02, 64.67,55.32, 39.62, 38.48; EIMS m/z 313 ([M]⁺).

(E)-1,2-Dichloro-4-(4-methoxystyryl)benzene (C45)

Isolated as an off-white solid (6.0 g, 53%): mp 91-94° C.; ¹H NMR (400MHz, CDCl₃) δ 7.56 (d, J=2.0 Hz, 1H), 7.46-7.42 (m, 2H), 7.39 (d, J=8.4Hz, 1H), 7.29 (dd, J=8.4, 2.1 Hz, 1H), 7.04 (d, J=16.2 Hz, 1H),6.93-6.88 (m, 2H), 6.85 (d, J=16.3 Hz, 1H), 3.84 (s, 3H); ¹³C NMR (101MHz, CDCl₃) δ 159.75, 137.86, 132.72, 130.58, 130.49, 130.12, 129.33,127.96, 127.77, 125.37, 123.98, 114.24, 55.35; EIMS m/z 279 ([M]⁺).

Example 6: Preparation of(E)-1-methoxy-4-(4-(trifluoromethyl)styryl)benzene (C46)

To a stirred solution of diethyl 4-methoxybenzyl phosphonate (8.89 g,34.0 mmol) in N,N-dimethylformamide (30 mL) was added sodium methoxidepowder (1.86 g, 34.0 mmol). The reaction mixture was stirred at roomtemperature for 1 hour. The reaction mixture was cooled to 0° C. and4-(trifluoromethyl)benzaldehyde (5.00 g, 28.0 mmol) inN,N-dimethylformamide (30 mL) was added dropwise. The reaction mixturewas stirred at 60° C. for 2 hours. The reaction mixture was poured inice cold water, filtered, and dried to afford the title compound as anoff-white solid (3.60 g, 80%): ¹H NMR (300 MHz, CDCl₃) δ 7.61-7.52 (m,4H), 7.47 (d, J=9.0 Hz, 2H), 7.14 (d, J=16.5 Hz, 1H), 6.97 (d, J=16.5Hz, 1H), 6.91 (d, J=9.0 Hz, 2H), 3.84 (s, 3H); ESIMS m/z 279 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 6:

(E)-1-(4-Methoxystyryl)-3-(trifluoromethyl)benzene (C47)

Isolated as an off-white solid (4.0 g, 85%): ¹H NMR (400 MHz, CDCl₃) δ7.72 (s, 1H), 7.64 (d, J=6.8 Hz, 1H), 7.50-7.44 (m, 4H), 7.12 (d, J=16.0Hz, 1H), 6.98 (d, J=16.0 Hz, 1H), 6.91 (d, J=8.8 Hz, 2H), 3.84 (s, 3H);ESIMS m/z 279 ([M+H]⁺).

(E)-2-Chloro-4-(4-methoxystyryl)-1-(trifluoromethoxy)benzene (C48)

Isolated: ESIMS m/z 329 ([M+H]⁺).

(E)-1-(4-Methoxystyryl)-3,5-bis(trifluoromethyl)benzene (C49)

Isolated as an off-white solid (4.0 g, 56%): ¹H NMR (300 MHz, CDCl₃) δ7.88 (s, 2H), 7.70 (s, 1H), 7.49 (d, J=8.4 Hz, 2H), 7.19 (d, J=16.5 Hz,1H), 6.99 (d, J=16.5 Hz, 1H), 6.92 (d, J=8.4 Hz, 2H), 3.84 (m, 3H);ESIMS m/z 347 ([M+H]⁺).

(E)-1,3-Dibromo-5-(4-methoxystyryl)benzene (C50)

Isolated as an off-white solid (2.2 g, 54%): ¹H NMR (300 MHz, CDCl₃) δ7.53 (s, 1H), 7.50 (s, 2H), 7.43 (d, J=9.0 Hz, 2H), 7.05 (d, J=16.2 Hz,1H), 6.90 (d, J=9.0 Hz, 2H), 6.79 (d, J=16.2 Hz, 1H), 3.80 (s, 3H);ESIMS m/z 367 ([M+H]⁺).

(E)-1-Chloro-3-(4-methoxystyryl)-5-(trifluoromethyl)benzene (C51)

Isolated as an off-white solid (4.3 g, 58%): ¹H NMR (300 MHz, CDCl₃) δ7.62 (s, 1H), 7.58 (s, 1H), 7.48-7.42 (m, 3H), 7.12 (d, J=16.2 Hz, 1H),6.95-6.85 (m, 3H), 3.84 (s, 3H); ESIMS m/z 313 ([M+H]⁺).

(E)-2-Bromo-1,3-dichloro-5-(4-methoxystyryl)benzene (C52)

Isolated as an off-white solid (2.8 g, 40%): ¹H NMR (300 MHz, CDCl₃) δ7.46 (s, 2H), 7.43 (d, J=9.0 Hz, 2H), 7.07 (d, J=13.5 Hz, 1H), 6.90 (d,J=9.0 Hz, 1H), 6.73 (d, J=13.5 Hz, 1H), 3.84 (s, 3H); ESIMS m/z 358([M+H]⁺).

(E)-1-Bromo-3-chloro-5-(4-methoxystyryl)benzene (C53)

Isolated as an off-white solid (4.0 g, 63%): ¹H NMR (300 MHz, CDCl₃) δ7.49 (s, 1H), 7.43 (d, J=8.4 Hz, 2H), 7.38 (s, 1H), 7.35 (s, 1H), 7.05(d, J=16.5 Hz, 1H), 6.91 (d, J=8.4 Hz, 2H), 6.80 (d, J=16.5 Hz, 1H),3.82 (s, 3H); ESIMS m/z 323 ([M+H]⁺).

(E)-1-Chloro-3-fluoro-5-(4-methoxystyryl)benzene (C54)

Isolated as an off-white solid (5.0 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ7.45 (d, J=8.4 Hz, 2H), 7.10-7.0 (m, 3H), 6.96-6.80 (m, 4H), 3.80 (s,3H); ESIMS m/z 263 ([M+H]⁺).

(E)-1-Chloro-2-fluoro-4-(4-methoxystyryl)benzene (C55)

Isolated as an off-white solid (7.0 g, 84%): ¹H NMR (400 MHz, CDCl₃) δ7.44 (d, J=8.0 Hz, 2H), 7.35-7.31 (m, 1H), 7.28-7.24 (m, 1H), 7.17 (dd,J=1.6, 8.0 Hz, 1H), 7.03 (d, J=16.0 Hz, 1H), 6.90 (d, J=8.0 Hz, 1H),7.49 (d, J=8.0 Hz, 1H), 6.86 (d, J=16.0 Hz, 1H), 3.82 (s, 3H); ESIMS m/z263 ([M+H]⁺).

(E)-2-Chloro-1-fluoro-4-(4-methoxystyryl)benzene (C56)

Isolated as an off-white solid (6.0 g, 72%): ESIMS m/z 263 ([M+H]⁺).

(E)-1-Chloro-3-(4-methoxystyryl)-5-methylbenzene (C57)

Isolated as an off-white solid (5.0 g, 60%): ¹H NMR (300 MHz, CDCl₃) δ7.44 (d, J=8.4 Hz, 2H), 7.28 (s, 1H), 7.15 (s, 1H), 7.05-7.00 (m, 2H),6.91-6.83 (m, 3H), 3.83 (s, 3H), 2.24 (s, 3H); ESIMS m/z 259 ([M+H]⁺).

(E)-1-Methoxy-4-(4-(perfluoroethyl)styryl)benzene (C58)

Isolated as an off-white solid (0.5 g, 42%): ¹H NMR (400 MHz, CDCl₃) δ7.60-7.50 (m, 4H), 7.47 (d, J=8.8 Hz, 2H), 7.15 (d, J=16.8 Hz, 1H), 6.98(d, J=16.8 Hz, 1H), 6.92 (d, J=8.8 Hz, 2H), 3.82 (s, 3H); ESIMS m/z 329([M+H]⁺).

(E)-1,2-bis(4-ethoxyphenyl)ethene (C59)

Isolated as an off-white solid (1.7 g, 34%): ¹H NMR (300 MHz, CDCl₃) δ7.40 (d, J=9.0 Hz, 4H), 6.91 (s, 2H), 6.87 (d, J=9.0 Hz, 4H), 4.05 (q,J=6.9 Hz, 4H), 1.42 (t, J=6.9 Hz, 6H); ESIMS m/z 269 ([M+H]⁺).

Example 7: Preparation of(E)-1,3-dichloro-2-fluoro-5-(4-methoxystyryl)benzene (C60)

A stirred mixture of 5-bromo-1,3-dichloro-2-fluorobenzene (2.00 g, 8.20mmol), 1-methoxy-4-vinylbenzene (1.32 g, 9.80 mmol), and triethylamine(20 mL) under argon was degassed for 5 minutes. Palladium(II) acetate(0.0368 g, 0.164 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (0.181g, 0.328 mmol) were added and the reaction was heated to 90° C. for 16hours. The reaction mixture was poured into water and extracted withethyl acetate. The combined organic layers were dried over sodiumsulfate, filtered, and concentrated. Purification by flash columnchromatography provided the title compound as an off-white solid (1.60g, 67%): ¹H NMR (300 MHz, CDCl₃) δ 7.41 (d, J=8.8 Hz, 2H), 7.31 (s, 1H),7.37 (s, 1H), 6.96 (d, J=16.0 Hz, 1H), 6.89 (d, J=8.8 Hz, 2H), 6.76 (d,J=16.0 Hz, 1H), 3.84 (s, 3H); ESIMS m/z 297 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 7:

(E)-1,3-Dichloro-5-(4-methoxystyryl)-2-methylbenzene (C61)

Isolated as an off-white solid (2.5 g, 67%): ¹H NMR (300 MHz, CDCl₃) δ7.43 (d, J=8.7 Hz, 2H), 7.38 (s, 2H), 7.02 (d, J=16.5 Hz, 1H), 6.90 (d,J=8.7 Hz, 2H), 6.79 (d, J=16.5 Hz, 1H), 3.82 (s, 3H), 2.42 (s, 3H);ESIMS m/z 293 ([M+H]⁺).

(E)-1,2-Dichloro-5-(4-methoxystyryl)-3-methylbenzene (C62)

Isolated as an off-white solid (3.0 g, 55%): ¹H NMR (300 MHz, CDCl₃) δ7.50-7.40 (m, 3H), 7.24 (s, 1H), 7.02 (d, J=15.9 Hz, 1H), 6.90 (d, J=9.0Hz, 2H), 6.81 (d, J=15.9 Hz, 1H), 3.83 (s, 3H), 2.42 (s, 3H); ESIMS m/z293 ([M+H]⁺).

Example 8: Preparation of (E)-1,2,4-trichloro-5-(4-methoxystyryl)benzene(C63)

To a sealed tube were added 1-bromo-2,4,5-trichlorobenzene (3.0 g, 12mmol), 1,2-dimethoxyethane:water (10:1, 30 mL),(E)-2-(4-methoxystyryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (C64)(3.7 g, 14 mmol), and potassium carbonate (3.2 g, 24 mmol). The reactionmixture was degassed for 10 minutes with argon, followed by addition oftetrakis(triphenylphosphine)palladium(O) (0.55 g, 0.48 mmol). Thereaction mixture was degassed for 10 minutes then heated at 90° C. for16 hours. The reaction mixture was poured in to water and extracted withethyl acetate. The combined organic layers were dried over sodiumsulfate, filtered, and concentrated. Purification by flash columnchromatography provided the title compound as an off-white solid (3.0 g,80%): ¹H NMR (400 MHz, CDCl₃) δ 7.73 (s, 1H), 7.50-7.45 (m, 3H), 7.20(d, J=16.0 Hz, 1H), 7.02 (d, J=16 Hz, 1H), 6.92 (d, J=8.0 Hz, 2H), 3.84(m, 3H); ESIMS m/z 313 ([M+H]⁺).

Example 9: Preparation of(E)-2-(4-methoxystyryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (C64)

To a 50 mL round-bottomed flask were added 1-ethynyl-4-methoxybenzene(4.0 g, 30 mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.3 g, 36mmol), zirconocene hydrochloride (1.2 g, 4.0 mmol), and triethylamine(2.8 mL, 15 mmol) at 0° C. The reaction mixture was then stirred at 65°C. for 16 hours. The reaction mixture was poured in water and extractedwith ethyl acetate. The combined organic layers were dried over sodiumsulfate, filtered, and concentrated. Purification by flash columnchromatography provided the title compound as an off-white semi solid(3.0 g, 38%): ¹H NMR (400 MHz, CDCl₃) δ 7.43 (d, J=8.8 Hz, 2H), 7.35 (d,J=18.0 Hz, 1H), 6.86 (d, J=8.8 Hz, 2H), 6.01 (d, J=18.0 Hz, 1H), 3.81(s, 3H), 1.30 (s, 12H).

Example 10: Preparation of 3,4,5-trichlorobenzaldehyde (C65)

In an oven dried, nitrogen flushed, 500 mL round-bottomed flask equippedwith a pressure equalizing addition funnel,5-bromo-1,2,3-trichlorobenzene (10.0 g, 38.4 mmol) was dissolved intetrahydrofuran (100 mL), and the resulting solution was cooled in anice bath under nitrogen. isoPropyl magnesium chloride (2 M solutiontetrahydrofuran, 21.1 mL, 42.3 mmol) was added dropwise with goodstirring over 15 minutes via the addition funnel. After 0.5 hours,N,N-dimethylformamide (3.72 mL, 48.0 mmol) was added to the darksolution with stirring. After an additional 0.5 hours, hydrochloric acid(1 N, 100 mL) was added with stirring. The layers were separated, andthe organic layer was washed with brine. The combined aqueous layerswere extracted with ether, and the combined organics were dried oversodium sulfate, filtered, and concentrated to afford the title compoundas a white solid (10:1 mixture of title compound to1,2,3-trichlorobenzene, 7.96 g, 99%): ¹H NMR (CDCl₃) δ 9.91 (s, 1H),7.88 (s, 2H); EIMS m/z 209 ([M]⁺).

Example 11: Preparation of 1-bromo-4-(perfluoroethyl)benzene (C66)

To a stirred solution of 1-(4-bromophenyl)-2,2,2-trifluoroethanone (5.00g, 19.7 mmol) in dichloromethane under argon were added4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (2.90 g, 11.8 mmol)and hydrogen fluoride pyridine complex (0.190 g, 9.80 mmol) at 0° C. Thereaction mixture was allowed to warm to room temperature and stirred for16 hours. The reaction mixture was poured into water and extracted withethyl acetate. The combined organic extracts were dried over sodiumsulfate, filtered, and concentrated. Purification by flash columnchromatograph provided the title compound as colorless liquid (1.00 g,20%): ¹H NMR (300 MHz, CDCl₃) δ 7.65 (d, J=9.0 Hz, 2H), 7.47 (d, J=9.0Hz, 2H); EIMS m/z 274 ([M]⁺).

Example 12: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxamido)benzoicacid (C67)

To a solution oftrans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxylic acid(C1) (0.300 g, 1.00 mmol) in dichloromethane (5.00 mL) stirred at 0° C.,were added N,N-dimethylformamide (1 drop) followed by oxalyl chloride(0.131 mL, 1.50 mmol) over 2 minutes. The ice batch was removed and thereaction allowed to warm to room temperature over 90 minutes. Thereaction was then concentrated to yield a yellow-orange semi-solid. Thesemi-solid was dissolved in dichloromethane (3.5 mL), and the solutionwas added slowly to a cooled solution of 5-amino-2-chlorobenzoic acid(0.206 g, 1.20 mmol) and triethylamine (0.209 mL, 1.50 mmol) indichloromethane (7 mL). The ice bath was removed and the reaction wasallowed to warm to room temperature over 90 minutes. The reaction wasdiluted with dichloromethane (10 mL) and washed with hydrochloric acid(0.1 N). The resulting slurry was filtered and the solid washed withwater. The precipitated solid was dried in a vacuum oven at 40° C. toprovide the title compound as a light brown solid (0.421 g, 93%): mp234-236° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 13.47 (s, 1H), 10.90 (s, 1H),8.16 (d, J=2.3 Hz, 1H), 7.78 (dd, J=8.7, 2.4 Hz, 1H), 7.59 (m, 4H), 3.56(dd, J=49.8, 8.5 Hz, 2H), 1.09 (m, 1H); ¹³C NMR (101 MHz, DMSO-d₆) δ166.26, 165.77, 162.61, 137.57, 137.27, 134.04, 132.18, 131.44, 131.22,127.88, 127.66, 126.40, 125.92, 122.88, 121.17, 102.37, 62.11, 38.41,36.83; ESIMS m/z 454 ([M+H]+).

Example 13: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F1)

5-Amino-2-chloro-N-(4-fluorophenyl)benzamide (C69) (0.174 g, 0.656 mmol)and 4-dimethylaminopyridine (0.087 g, 0.711 mmol) were sequentiallyadded to a stirred mixture oftrans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxylic acid(C1) (0.164 g, 0.547 mmol) and1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.157 g,0.820 mmol) in 1,2-dichloroethane (5.5 mL) at room temperature. Thereaction was stirred at room temperature for 20 hours. The reaction wasdiluted with dichloromethane, washed with saturated aqueous sodiumbicarbonate (2×), and washed with hydrochloric acid (1 N) (2×). Theorganic phase was dried over magnesium sulfate, filtered, andconcentrated. Purification by flash column chromatography using 0-100%ethyl acetate/hexanes as eluent provided the title compound as a whitefoam (0.138 g, 46%).

The following compounds were prepared in like manner to the procedureoutlined in Example 13:

trans-3-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F2)

Isolated as a brown solid (0.106 g, 79%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-(trifluoromethyl)benzamide(F3)

Isolated as a yellow solid (0.074 g, 34%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-iodobenzamide(F4)

Isolate as a brown solid (0.078 g, 50%).

trans-2-Chloro-N-(4-cyanophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F5)

Isolated as a yellow solid (0.081 g, 39%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(trifluoromethyl)phenyl)benzamide(F6)

Isolated as a yellow solid (0.082 g, 49%).

trans-2-Chloro-N-(4-chlorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F7)

Isolated as a yellow solid (0.083 g, 47%).

trans-2-Chloro-N-(2-chloro-4-fluorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F8)

Isolated as a yellow solid (0.075 g, 42%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(o-tolyl)benzamide(F9)

Isolated as a brown solid (0.104 g, 54%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-methylbenzamide(F10)

Isolated as a white solid (0.095 g, 50%).

trans-2-Bromo-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F11)

Isolated as a red solid (0.085 g, 51%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-(1H-1,2,4-triazol-1-yl)benzamide(F12)

Isolated as a brown solid (0.103 g, 60%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F13)

Isolated as a white powder (0.090 g, 79%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F14)

Isolated as an off-white powder (0.155 g, 77%).

trans-3-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)benzamide(F15)

Isolated as a yellow oil (0.025 g, 18%).

trans-2-Chloro-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-phenylbenzamide(F16)

Isolated as a white solid (0.092 g, 66%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-fluorophenyl)benzamide(F17)

Isolated as a white solid (0.030 g, 21%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F18)

Isolated as a white solid (0.108 g, 72%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorphenyl)-N-methylbenzamide(F19)

Isolated as a white solid (0.137 g, 92%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-fluorophenyl)benzamide(F20)

Isolated as a pink solid (0.115 g, 79%).

trans-2-Chloro-N-(3-cyanophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F21)

Isolated as a white solid (0.113 g, 76%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,3-difluorophenyl)benzamide(F22)

Isolated as a white solid (0.120 g, 79%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,4-difluorophenyl)benzamide(F23)

Isolated as a white solid (0.121 g, 80%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4,6-trifluorophenyl)benzamide(F24)

Isolated as a light pink solid (0.109 g, 70%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F25)

Isolated as a light pink solid (0.092 g, 61%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(pyridin-4-yl)benzamide(F26)

Isolated as a white solid (0.112 g, 64%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(pyridin-3-yl)benzamide(F27)

Isolated as a white solid (0.138 g, 78%).

trans-5-(2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)benzamide(F28)

Isolated as a white solid (0.130 g, 92%).

trans-5-(2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)benzamide(F29)

Isolated as a white solid (0.121 g, 90%).

trans-3-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-methoxybenzamide(F30)

Isolated as a yellow solid (0.069 g, 47%).

trans-2-Chloro-N-(2-chloropyridin-3-yl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F31)

Isolated as a white solid (0.126 g, 67%).

trans-2-Chloro-N-(6-chloropyridin-3-yl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F32)

Isolated as a white solid (0.131 g, 70%).

trans-2-Chloro-N-(6-cyanopyridin-3-yl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F33)

Isolated as a white solid (0.094 g, 51%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-fluorophenyl)-N-methylbenzamide(F34)

Isolated as a white solid (0.119 g, 80%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-fluorophenyl)-N-methylbenzamide(F35)

Isolated as a white solid (0.123 g, 82%).

trans-2-Chloro-N-(4-cyano-2-methylphenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F36)

Isolated as a white solid (0.103 g, 68%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-methylphenyl)benzamide(F37)

Isolated as a white solid (0.112 g, 75%).

trans-2-Chloro-N-(2-chlorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F38)

Isolated as a white foam (0.101 g, 77%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F39)

Isolated as a white foam (0.096 g, 68%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F40)

Isolated as a white solid (0.104 g, 77%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-isopropylphenyl)benzamide(F41)

Isolated as a white solid (0.104 g, 78%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-ethyl-6-methylphenyl)benzamide(F42)

Isolated as a white solid (0.103 g, 77%).

trans-2-Chloro-N-(3-chlorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F43)

Isolated as a white solid (0.029 g, 22%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-N-methylbenzamide(F44)

Isolated as a white foam (0.082 g, 57%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)-N-methylbenzamide(F45)

Isolated as a white solid (0.077 g, 57%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(3-fluorophenyl)-N-methylbenzamide(F46)

Isolated as a white solid (0.096 g, 70%).

trans-3-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)-N-methylbenzamide(F47)

Isolated as a yellow glass (0.106 g, 78%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-4-fluoro-N-(4-fluorophenyl)benzamide(F48)

Isolated as a yellow foam (0.083 g, 59%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2,4-difluoro-N-(4-fluorophenyl)benzamide(F49)

Isolated as a white solid (0.061 g, 45%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-fluorophenyl)benzamide(F50)

Isolated as a white solid (0.108 g, 83%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-fluorophenyl)benzamide(F51)

Isolated as a white solid (0.104 g, 76%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F52)

Isolated as a white solid (0.113 g, 85%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F53)

Isolated as a white solid (0.094 g, 67%).

trans-2-Chloro-N-(4-cyano-2-methylphenyl)-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F54)

Isolated as a white solid (0.085 g, 63%).

trans-2-Chloro-N-(4-cyano-2-methylphenyl)-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F55)

Isolated as a white solid (0.088 g, 62%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F56)

Isolated as a white solid (0.120 g, 78%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F57)

Isolated as a white solid (0.102 g, 61%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F58)

Isolated as a white solid (0.066 g, 42%).

trans-5-(2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)-N-methylbenzamide(F59)

Isolated as a white solid (0.117 g, 86%).

trans-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)-N-methylbenzamide(F60)

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluorobenzamide(F61)

Isolated as a white solid (0.120 g, 73%).

trans-5-(2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluorobenzamide(F62)

Isolated as a white solid (0.102 g, 62%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluoro-N-methylbenzamide(F63)

Isolated as a white solid (0.123 g, 73%).

trans-5-(2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluoro-N-methylbenzamide(F64)

Isolated as a white foam (0.110 g, 65%).

trans-5-(2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluoro-N-methylbenzamide(F65)

Isolated as a white solid (0.098 g, 55%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-methyl-N-phenylbenzamide(F66)

Isolated as a white foam (0.123 g, 78%).

trans-5-(2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-methyl-N-phenylbenzamide(F67)

Isolated as a white foam (0.124 g, 79%).

trans-5-(2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-methyl-N-phenylbenzamide(F68)

Isolated as a white solid (0.122 g, 72%).

trans-3-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-methyl-N-phenylbenzamide(F69)

Isolated as a yellow foam (0.101 g, 64%).

trans-3-(2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-methyl-N-phenylbenzamide(F70)

Isolated as a light yellow foam (0.107 g, 68%).

trans-3-(2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-methyl-N-phenylbenzamide(F71)

Isolated as a light yellow foam (0.114 g, 68%).

trans-5-(3-(4-Bromo-3,5-dichlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide(F72)

Isolated as a white solid (0.030 g, 22%).

trans-2-Chloro-5-(2,2-dichloro-3-(2,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F73)

Isolated as a white solid (0.047 g, 32%).

trans-2-Chloro-5-(2,2-dichloro-3-(2,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F74)

Isolated as a white solid (0.109 g, 73%).

trans-5-(2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-2-fluorobenzamide(F75)

Isolated as a white solid (0.098 g, 56%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-fluoropyridin-2-yl)benzamide(F76)

Isolated as a white solid (0.029 g, 23%).

trans-5-(2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-N-methylpicolinamide(F77)

Isolated as a white solid (0.039 g, 25%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(pyridin-2-yl)benzamide(F78)

Isolated as a white solid (0.071 g, 51%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-(trifluoromethoxy)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F79)

Isolated as a white solid (0.082 g, 57%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-(trifluoromethoxy)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F80)

Isolated as a white solid (0.111 g, 75%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F81)

Isolated as a white solid (0.123 g, 80%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F82)

Isolated as a white solid (0.130 g, 82%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F83)

Isolated as a white solid (0.082 g, 52%).

trans-5-(3-(3,5-Bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide(F84)

Isolated as a white solid (0.042 g, 30%).

trans-5-(3-(3,5-Bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)-N-methylbenzamide(F85)

Isolated as a white solid (0.092 g, 64%).

trans-5-(3-(3,5-Bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,6-difluorophenyl)benzamide(F86)

Isolated as a white solid (0.038 g, 26%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F87)

Isolated as a white solid (0.055 g, 38%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F88)

Isolated as a white solid (0.095 g, 63%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F89)

Isolated as a white solid (0.032 g, 21%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dibromophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F90)

Isolated as a white solid (0.023 g, 16%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dibromophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F91)

Isolated as a white solid (0.066 g, 47%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dibromophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F92)

Isolated as a white solid (0.020 g, 14%).

trans-N-(4-Cyano-2-fluorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide(F93)

Isolated as a white solid (0.108 g, 78%).

trans-N-(4-Cyano-2-fluorophenyl)-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide(F94)

Isolated as a white solid (0.122 g, 88%).

trans-N-(4-Cyano-2-fluorophenyl)-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2-fluorobenzamide(F95)

Isolated as a white solid (0.013 g, 10%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F96)

Isolated as a white solid (0.017 g, 11%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F97)

Isolated as a white solid (0.063 g, 41%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F98)

Isolated as a white solid (0.025 g, 16%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-ethyl-N-(4-fluorophenyl)benzamide(F99)

Isolated as a white solid (0.087 g, 60%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-(2,2,2-trifluoroethyl)benzamide(F100)

Isolated as a white solid (0.095 g, 60%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-propylbenzamide(F101)

Isolated as a yellow foam (0.090 g, 61%).

trans-N-Allyl-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F102)

Isolated as an orange foam (0.047 g, 32%).

trans-2-chloro-N-(4-cyano-2-fluorophenyl)-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F103)

Isolated as a colorless oil (0.032 g, 22%).

trans-2-Chloro-N-(4-cyano-2-fluorophenyl)-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F104)

Isolated as a white foam (0.016 g, 11%).

trans-N-(4-Cyano-2-fluorophenyl)-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-methylbenzamide(F105)

Isolated as a white foam (0.020 g, 20%).

trans-2-Chloro-N-(4-cyano-2-fluorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-methylbenzamide(F106)

Isolated as a colorless oil (0.041 g, 28%).

trans-2-Chloro-N-(4-cyano-2-fluorophenyl)-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-methylbenzamide(F107)

Isolated as a white foam (0.034 g, 23%).

trans-2-Chloro-N-(4-cyano-2-fluorophenyl)-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-methylbenzamide(F108)

Isolated as a colorless oil (0.039 g, 25%).

trans-2-Chloro-5-(2,2-dichloro-3-phenylcyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F109)

Isolated as a yellow film (0.011 g, 6%).

trans-2-Chloro-5-(2,2-dichloro-3-phenylcyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F110)

Isolated as a yellow solid (0.044 g, 25%).

trans-2-Chloro-5-(2,2-dichloro-3-phenylcyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F11)

Isolated as a yellow film (0.011 g, 6%).

trans-2,2-Dichloro-N-(4-chloro-3-((4-fluorophenyl)(methyl)carbamothioyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide(F112)

Isolated as a yellow solid (0.024 g, 25%).

trans-2,2-Dichloro-N-(4-chloro-3-((4-fluorophenyl)carbamothioyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide(F113)

Isolated as a yellow solid (0.027 g, 13%).

trans-N-(4-Cyano-2-fluorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-methylbenzamide(F114)

Isolated as a colorless glass (0.004 g, 4%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-(methylthio)benzamide(F115)

Isolated as a white solid (0.173 g, 28%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-5-methylphenyl)cyclopropane-1-carboxamido)-N(4-fluorophenyl)benzamide(F116)

Isolated as a white solid (0.083 g, 59%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-5-methylphenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F117)

Isolated as a white foam (0.100 g, 69%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-5-methylphenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F118)

Isolated as a white foam (0.066 g, 45%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methylphenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F119)

Isolated as a white foam (0.028 g, 21%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methylphenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F120)

Isolated as a white solid (0.077 g, 56%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methylphenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F121)

Isolated as a white foam (0.025 g, 18%).

trans-2-Chloro-5-(2,2-dibromo-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F122)

Isolated as an off-white solid (0.075 g, 45%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-methylphenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F123)

Isolated as a white foam (0.102 g, 76%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-methylphenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F124)

Isolated as a white foam (0.071 g, 52%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichloro-5-methylphenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F125)

Isolated as a white foam (0.094 g, 68%).

Example 14: Preparation oftrans-4-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)picolinamide(F126)

To a solution oftrans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxylic acid(C1) (0.100 g, 0.333 mmol) in dichloromethane (3.33 mL) at 0° C. wasadded N,N-dimethylformamide (1 drop) and oxalyl chloride (0.0440 mL,0.500 mmol) dropwise. The cold bath was removed and the reaction wasstirred at room temperature for 1 hour. The reaction was again cooled to0° C., and N-methylmorpholine (0.110 mL, 1.000 mmol) followed by4-amino-N-(4-fluorophenyl)picolinamide (C81) (0.154 g, 0.667 mmol) wereadded. The reaction was stirred at room temperature for 1 hour. Thereaction was diluted with dichloromethane, washed with saturated aqueoussodium bicarbonate (2×), and washed with hydrochloric acid (1 N) (2×).The organic phase was dried over magnesium sulfate, filtered, andconcentrated. Purification by flash column chromatography using 0-100%ethyl acetate/hexanes as eluent provided the title compound as a glassyclear solid (0.0800 g, 44%).

The following compounds were prepared in like manner to the procedureoutlined in Example 14:

trans-2-Chloro-3-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F127)

Isolated as a white solid (0.102 g, 67%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-methoxybenzamide(F128)

Isolated as a white solid (0.040 g, 26%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-fluoro-N-(4-fluorophenyl)enylbenzamide(F129)

Isolated as a white solid (0.081 g, 58%).

trans-4-Chloro-3-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F130)

Isolated as an off-white solid (0.099 g, 65%).

trans-3-Chloro-6-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)picolinamide(F131)

Isolated as a faint yellow solid (0.116 g, 75%).

trans-2-Cyano-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F132)

Isolated as a yellow film (0.043 g, 38%).

trans-6-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)picolinamide(F133)

Isolated as a clear glassy solid (0.033 g, 40%).

trans-3-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-4-methylbenzamide(F134)

Isolated as an off-white solid (0.039 g, 35%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-(trifluoromethoxy)benzamide(F135)

Isolated as a white solid (0.108 g, 65%).

trans-3-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F136)

Isolated as a clear glassy solid (0.078 g, 51%).

Example 15: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-nitrophenyl)benzamide(F137)

To a solution of 4-nitroaniline (0.0270 g, 0.198 mmol) indichloromethane (2 mL) was added in sequence1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.0480 g,0.248 mmol), 4-dimethylaminopyridine (0.0240 g, 0.198 mmol), andtrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxamido)benzoicacid (C67) (0.0750 g, 0.165 mmol). The reaction was stirred at roomtemperature for 16 hours. The reaction was loaded onto Celite®, andpurification by flash column chromatography using 0-25% ethylacetate/hexanes as eluent provided the title compound as a yellow solid(0.0131 g, 14%).

The following compounds were prepared in like manner to the procedureoutlined in Example 15:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1,2,3-thiadiazol-5-yl)benzamide(F138)

Isolated as a white solid (0.024 g, 27%).

Example 16: Preparation oftrans-3-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)pyridine1-oxide (F139)

To a solution oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(pyridin-3-yl)benzamide(F27) (0.0930 g, 0.176 mmol) in dichloromethane (4 mL) was addedmeta-chloroperoxybenzoic acid (0.0404 g, 0.176 mmol). The reaction wasstirred at room temperature for 14 hours. Celite® was added to thereaction and the solvent was concentrated. Purification by flash columnchromatography using 0-10% methanol/dichloromethane as eluent providedthe title compound as a white solid (0.0813 g, 85%).

The following compounds were prepared in like manner to the procedureoutlined in Example 16:

trans-4-(2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)pyridine1-oxide (F140)

Isolated as a white solid (0.035 g, 34%).

trans-4-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-((4-fluorophenyl)carbamoyl)pyridine1-oxide (F141)

Isolated as a faint yellow solid (0.038 g, 58%).

Example 17: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(6-fluoropyridin-3-yl)benzamide(F142)

6-Fluoropyridin-3-amine (0.0290 g, 0.254 mmol) was dissolved indichloromethane (2 mL). The solution was cooled in an ice bath.Triethylamine (0.0440 mL, 0.318 mmol) was added.trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoylchloride (C68) (0.100 g, 0.212 mmol) was dissolved in dichloromethane (2mL), and the solution was added to the reaction mixture. The ice bathwas removed and the reaction allowed to stir overnight at roomtemperature. The reaction was loaded onto Celite® and purified by flashcolumn chromatography using 0-40% ethyl acetate/hexanes as eluent toafford the title compound as a white solid (0.0339 g, 29%).

The following compounds were prepared in like manner to the procedureoutlined in Example 17:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(methylsulfonyl)phenyl)benzamide(F143)

Isolated as a white solid (0.040 g, 30%).

trans-2-Chloro-N-(4-cyano-2-fluorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F144)

Isolated as a white solid (0.028 g, 23/).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(oxazol-2-yl)benzamide(F145)

Isolated as a light brown solid (0.021 g, 19%).

Example 18: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-methoxyphenyl)benzamide(F146)

To a solution oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxamido)benzoicacid (C67) (0.100 g, 0.212 mmol) in dichloromethane (0.1 mL) was addedN,N-dimethylformamide (one drop), and the reaction cooled in an icebath. Oxalyl chloride (0.0438 mL, 0.254 mmol) was charged slowly overabout 5 minutes. The reaction was removed the ice bath and allowed towarm to room temperature over 90 minutes. The reaction was thenconcentrated. The residue was re-dissolved in dichloromethane (0.1 mL).This solution was added to a cooled (ice bath) separate solution of4-methoxyaniline (0.0310 g, 0.254 mmol) and triethylamine (0.0440 mL,0.318 mmol) in dichloromethane (0.5 mL). The reaction was removed theice bath and stirred at room temperature for 14 hours. The reaction wasadsorbed directly onto Celite® and purified by flash columnchromatography using ethyl acetate/hexanes as eluent followed bytrituration with dichloromethane/hexanes to provide the title compoundas a white solid (0.0666 g, 56%).

The following compounds were prepared in like manner to the procedureoutlined in Example 18:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(trifluoromethoxy)phenyl)benzamide(F147)

Isolated as a yellow solid (0.078 g, 60%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(difluoromethoxy)phenyl)benzamide(F148)

Isolated as a light brown solid (0.089 g, 70%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(methylthio)phenyl)benzamide(F149)

Isolated as a light brown solid (0.068 g, 56%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoro-4-methoxyphenyl)benzamide(F150)

Isolated as a beige solid (0.060 g, 49%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoro-4-methylphenyl)benzamide(F151)

Isolated as a white solid (0.057 g, 48%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(methylcarbamoyl)phenyl)benzamide(F152)

Isolated as a white solid (0.062 g, 50%).

trans-N-(4-Acetamidophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F153)

Isolated as a white solid (0.096 g, 77%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluorophenyl)benzamide(F154)

Isolated as a white solid (0.044 g, 37%).

trans-2,2-Dichloro-N-(4-chloro-3-(5-fluoroindoline-1-carbonyl)phenyl)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide(F155)

Isolated as a white foam (0.052 g, 41%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoropyridin-3-yl)benzamide(F156)

Isolated as a white solid (0.058 g, 48%).

Example 19: Preparation oftrans-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-(methylsulfonyl)benzamide(F157)

To a solution oftrans-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-(methylthio)benzamide(F115) (0.049 g, 0.088 mmol) in dichloromethane (0.878 mL) was addedmeta-chloroperoxybenzoic acid (0.049 g, 0.22 mmol). The reaction wasstirred at room temperature for 3 hours. Saturated aqueous sodiumbicarbonate was added, and the mixture was extracted with ethyl acetate.The combined organic phases were washed with brine, dried over magnesiumsulfate, filtered, and concentrated. Purification by flash columnchromatography using 0-15% methanol/dichloromethane as eluent providedthe title compound as a white solid (0.042 g, 73%).

Example 20: Preparation oftrans-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-(methylsulfinyl)benzamide(F158)

To a solution oftrans-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-2-(methylthio)benzamide(F115) (0.051 g, 0.091 mmol) in dichloromethane (0.9 mL) was addedmeta-chloroperoxybenzoic acid (0.021 g, 0.096 mmol). The reaction wasstirred at room temperature for 1 hour. Saturated aqueous sodiumbicarbonate was added, and the mixture was extracted with ethyl acetate.The combined organic phases were washed with brine, dried over magnesiumsulfate, filtered, and concentrated. Purification by flash columnchromatography using 0-15% methanol/dichloromethane as eluent providedthe title compound as a white solid (0.036 g, 65%).

The following compounds were prepared in like manner to the procedureoutlined in Example 20:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(methylsulfinyl)phenyl)benzamide(F159)

Isolated as a white solid (0.013 g, 24%).

Example 21: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoylchloride (C68)

To a solution oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxamido)benzoicacid (C67) (0.200 g, 0.441 mmol) in dichloromethane (2.2 mL) stirred at0° C. was added N,N-dimethylformamide (1 drop) followed by oxalylchloride (0.0579 mL, 0.661 mmol) over 2 minutes. The ice batch wasremoved, and the reaction allowed to warm to room temperature over 90minutes. The reaction was then concentrated to provide the titlecompound as a cream colored foam which was used without furtherpurification or characterization (0.211 g, quant).

Example 22: Preparation of 5-amino-2-chloro-N-(4-fluorophenyl)benzamide(C69) and 3-amino-N-(4-fluorophenyl)benzamide (C70)

Palladium on alumina (5%, 0.0065 g, 0.061 mmol) was added to adeoxygenated solution of 2-chloro-N-(4-fluorophenyl)-5-nitrobenzamide(C143) (0.18 g, 0.61 mmol) in ethyl acetate (6 mL) at room temperature.The mixture was purged with nitrogen, and the reaction was stirred undera balloon of hydrogen at room temperature for 3 hours. Palladium oncarbon (10%, 0.0070 g) was added, and the reaction was stirred under aballoon of hydrogen overnight. The reaction was diluted withdichloromethane, and the reaction was washed with hydrochloric acid (1N). The aqueous layer was neutralized with saturated aqueous sodiumbicarbonate and extracted with dichloromethane to provide (C69) as ayellow oil (0.028 g, 16%): ¹H NMR (400 MHz, CDCl₃) δ 8.09 (s, 1H),7.65-7.51 (m, 2H), 7.17 (d, J=8.6 Hz, 1H), 7.08-7.00 (m, 3H), 6.68 (dd,J=8.6, 2.9 Hz, 1H), 3.85 (s, 2H); IR (thin film) 3349, 1654 cm⁻¹; ESIMSm/z 265 ([M+H]⁺). The organic layer was concentrated to a give a yellowsolid, which was suspended in degassed methanol (6 mL). Palladium oncarbon (10%, 0.010 g) was added, and the reaction was stirred under aballoon of hydrogen overnight. The reaction was diluted with ethylacetate and extracted with hydrochloric acid (1 N). The aqueous layerwas basified with saturated aqueous sodium bicarbonate, extracted withdichloromethane, and concentrated to provide (C70) as a yellow solid(0.060 g, 38%): ¹H NMR (400 MHz, CDCl₃) δ 7.85 (s, 1H), 7.58 (dd, J=9.0,4.8 Hz, 2H), 7.25-7.20 (m, 1H), 7.20-7.15 (m, 1H), 7.04 (t, J=8.7 Hz,2H), 6.83 (ddd, J=7.9, 2.4, 0.9 Hz, 1H), 3.83 (s, 2H); IR (thin film)3328, 1648 cm⁻¹; ESIMS m/z 231 ([M+H]⁺).

Example 23: Preparation of 5-amino-2-chloro-N-(4-fluorophenyl)benzamide(C69)

To a solution of 2-chloro-N-(4-fluorophenyl)-5-nitrobenzamide (C143)(3.57 g, 12.1 mmol) in methanol (81 mL) and water (40.4 mL) was addediron powder (3.38 g, 60.6 mmol) and ammonium chloride (1.94 g, 36.3mmol). The reaction was heated at 60° C. for 2 hours. The reaction wasfiltered through Celite®. The filtrate was diluted with ethyl acetateand washed with brine. The organic phase was extracted with hydrochloricacid (1 N). The combined aqueous phases were neutralized with saturatedaqueous sodium bicarbonate and extracted with dichloromethane. Thecombined organic phases were dried over magnesium sulfate, filtered, andconcentrated to provide the title compound as a white solid (1.75 g,54%).

The following compounds were prepared in like manner to the procedureoutlined in Example 23:

5-Amino-N-(4-fluorophenyl)-2-(trifluoromethyl)benzamide (C71)

Isolated as a brown solid (0.182 g, 63%): ¹H NMR (400 MHz, DMSO-d₆) δ10.47 (s, 1H), 7.79-7.62 (m, 2H), 7.41 (d, J=8.3 Hz, 1H), 7.18 (t, J=8.9Hz, 2H), 6.77-6.62 (m, 2H), 6.06 (s, 2H); EIMS m/z 298 ([M]⁺).

5-Amino-N-(4-fluorophenyl)-2-iodobenzamide (C72)

Isolated as a brown solid (0.205 g, 84%): ¹H NMR (400 MHz, DMSO-d₆) δ10.34 (s, 1H), 7.78-7.66 (m, 2H), 7.45 (d, J=8.5 Hz, 1H), 7.24-7.10 (m,2H), 6.67 (d, J=2.7 Hz, 1H), 6.45 (dd, J=8.5, 2.7 Hz, 1H), 5.50 (s, 2H);IR (thin film) 3247, 1650 cm⁻¹; ESIMS m/z 357 ([M+H]⁺).

5-Amino-2-chloro-N-(4-cyanophenyl)benzamide (C73)

Isolated as a yellow solid (0.119 g, 52%): ¹H NMR (400 MHz, DMSO-d₆) δ10.83 (s, 1H), 7.90 (d, J=8.7 Hz, 2H), 7.81 (d, J=8.8 Hz, 2H), 7.15 (d,J=8.6 Hz, 1H), 6.71 (d, J=2.7 Hz, 1H), 6.67 (dd, J=8.6, 2.7 Hz, 1H),5.51 (s, 2H); IR (thin film) 3365, 3100, 2223, 1670 cm⁻¹; ESIMS m/z 273([M+H]⁺).

5-Amino-2-chloro-N-(4-(trifluoromethyl)phenyl)benzamide (C74)

Isolated as a yellow solid (0.253 g, 79%): ¹H NMR (400 MHz, DMSO-d₆) δ10.76 (s, 1H), 7.93 (d, J=8.5 Hz, 2H), 7.72 (d, J=8.6 Hz, 2H), 7.15 (d,J=8.6 Hz, 1H), 6.72 (d, J=2.7 Hz, 1H), 6.67 (dd, J=8.6, 2.7 Hz, 1H),5.51 (s, 2H); IR (thin film) 3230, 3039, 1666 cm⁻¹; ESIMS m/z 316([M+H]⁺).

5-Amino-2-chloro-N-(4-chlorophenyl)benzamide (C75)

Isolated as a yellow solid (0.290 g, 90%): ¹H NMR (400 MHz, DMSO-d₆) δ10.51 (s, 1H), 7.80-7.68 (m, 2H), 7.44-7.32 (m, 2H), 7.13 (d, J=8.6 Hz,1H), 6.69 (d, J=2.7 Hz, 1H), 6.65 (dd, J=8.6, 2.8 Hz, 1H), 5.48 (s, 2H);IR (thin film) 3375, 3212, 1660 cm⁻¹; ESIMS m/z 282 ([M+H]⁺).

5-Amino-2-chloro-N-(2-chloro-4-fluorophenyl)benzamide (C76)

Isolated as a white solid (0.092 g, 68%): IR (thin film) 3377, 3157,1659 cm⁻¹; ESIMS m/z 300 ([M+H]⁺).

5-Amino-2-chloro-N-(4-chlorophenyl)benzamide (C77)

Isolated as a red solid (0.185 g, 84%): ¹H NMR (400 MHz, DMSO-d₆) δ 9.82(s, 1H), 7.35 (d, J=7.5 Hz, 1H), 7.26-7.10 (m, 4H), 6.75 (d, J=2.7 Hz,1H), 6.63 (dd, J=8.6, 2.7 Hz, 1H), 5.46 (s, 2H), 2.27 (s, 3H); IR (thinfilm) 3351, 3228, 1654 cm⁻¹; ESIMS m/z 262 ([M+H]⁺).

5-Amino-N-(4-fluorophenyl)-2-methylbenzamide (C78)

Isolated as a brown solid (0.390 g, 83%): ¹H NMR (400 MHz, DMSO-d₆) δ10.23 (s, 1H), 7.82-7.68 (m, 2H), 7.23-7.08 (m, 2H), 6.92 (d, J=8.2 Hz,1H), 6.65 (d, J=2.4 Hz, 1H), 6.58 (dd, J=8.1, 2.4 Hz, 1H), 5.07 (s, 2H),2.18 (s, 3H); IR (thin film) 3422, 3339, 3256, 1649 cm⁻¹; ESIMS m/z 245([M+H]⁺).

5-Amino-2-bromo-N-(4-fluorophenyl)benzamide (C79)

Isolated as a brown solid (0.308 g, 87%): ¹H NMR (400 MHz, DMSO-d₆) δ10.40 (s, 1H), 7.76-7.66 (m, 2H), 7.26 (d, J=8.6 Hz, 1H), 7.21-7.11 (m,2H), 6.68 (d, J=2.7 Hz, 1H), 6.58 (dd, J=8.6, 2.8 Hz, 1H), 5.50 (s, 2H);IR (thin film) 3382, 3236, 1645 cm⁻¹; ESIMS m/z 310 ([M+H]⁺).

5-Amino-N-(4-fluorophenyl)-2-(1H-1,2,4-triazol-1-yl)benzamide (C80)

Isolated as a beige solid (0.182 g, 54%): ¹H NMR (400 MHz, DMSO-d₆) δ10.32 (s, 1H), 8.63 (s, 1H), 7.99 (s, 1H), 7.59-7.51 (m, 2H), 7.24 (d,J=8.5 Hz, 1H), 7.15-7.08 (m, 2H), 6.81 (d, J=2.5 Hz, 1H), 6.74 (dd,J=8.5, 2.5 Hz, 1H), 5.75 (s, 2H); IR (thin film) 3344, 3227, 3051, 1659cm⁻¹; ESIMS m/z 298 ([M+H]⁺).

4-Amino-N-(4-fluorophenyl)picolinamide (C81)

Isolated as a brown solid (0.321 g, 57%): ¹H NMR (400 MHz, DMSO-d₆) δ10.53 (s, 1H), 8.11 (d, J=5.5 Hz, 1H), 7.91 (dd, J=9.0, 5.0 Hz, 2H),7.32 (d, J=2.1 Hz, 1H), 7.18 (t, J=8.9 Hz, 2H), 6.66 (dd, J=5.5, 2.2 Hz,1H), 6.44 (s, 2H); IR (thin film) 3484, 3359, 3321, 3234, 1642 cm⁻¹;ESIMS m/z 232 ([M+H]⁺).

3-Amino-2-chloro-N-(4-fluorophenyl)benzamide (C82)

Isolated as a yellow solid (0.332 g, 65%): ¹H NMR (400 MHz, DMSO-d₆) δ10.42 (s, 1H), 7.81-7.65 (m, 2H), 7.25-7.13 (m, 2H), 7.10 (t, J=7.7 Hz,1H), 6.88 (dd, J=8.1, 1.3 Hz, 1H), 6.67 (dd, J=7.3, 1.3 Hz, 1H), 5.57(s, 2H); IR (thin film) 3372, 3237, 3011, 1655 cm⁻¹; ESIMS m/z 265([M+H]⁺).

5-Amino-N-(4-fluorophenyl)-2-methoxybenzamide (C83)

Isolated as a light brown solid (0.356 g, 61%): ¹H NMR (400 MHz,DMSO-d₆) δ 10.12 (s, 1H), 7.80-7.69 (m, 2H), 7.21-7.11 (m, 2H), 6.96 (d,J=2.9 Hz, 1H), 6.90 (d, J=8.8 Hz, 1H), 6.71 (dd, J=8.7, 2.9 Hz, 1H),4.89 (s, 2H), 3.79 (s, 3H); IR (thin film) 3338, 1662 cm⁻¹; ESIMS m/z261 ([M+H]⁺).

5-Amino-2-chloro-N-phenylbenzamide (C84)

Isolated as a white foam (1.28 g, 96%): ¹H NMR (400 MHz, CDCl₃) δ 7.97(s, 1H), 7.68-7.60 (m, 2H), 7.43-7.34 (m, 2H), 7.22-7.13 (m, 2H), 7.10(d, J=2.9 Hz, 1H), 6.71 (dd, J=8.5, 2.9 Hz, 1H), 3.83 (s, 2H); ¹³C NMR(101 MHz, CDCl₃) δ 164.43, 145.71, 137.61, 135.33, 131.12, 129.12,124.77, 120.12, 118.92, 118.22, 116.55; ESIMS m/z 247 ([M+H]⁺).

5-Amino-2-chloro-N-(2-fluorophenyl)benzamide (C85)

Isolated as a white solid (1.24 g, quant): ¹H NMR (400 MHz, CDCl₃) δ8.48 (td, J=8.1, 1.6 Hz, 1H), 8.34 (s, 1H), 7.23-7.08 (m, 5H), 6.72 (dd,J=8.5, 2.9 Hz, 1H), 3.85 (s, 2H), 3.48 (s, 1H); ¹⁹F NMR (376 MHz, CDCl₃)δ −130.65; ESIMS m/z 265 ([M+H]⁺).

5-Amino-2-chloro-N-(2,4-difluorophenyl)benzamide (C86)

Isolated as a purple solid (0.37 g, 28%): ¹H NMR (400 MHz, CDCl₃) δ 8.42(tdd, J=9.7, 6.0, 3.6 Hz, 1H), 8.25 (s, 1H), 7.21 (d, J=8.5 Hz, 1H),7.13 (d, J=2.9 Hz, 1H), 6.97-6.88 (m, 2H), 6.73 (dd, J=8.5, 2.9 Hz, 1H),3.84 (s, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −114.57 (d, J=4.6 Hz), −125.78(d, J=4.6 Hz); ESIMS m/z 283 ([M+H]⁺).

5-Amino-2-chloro-N-(4-fluorophenyl)-N-methylbenzamide (C87)

Isolated as a white solid (0.81 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ7.17-7.07 (m, 2H), 6.96-6.83 (m, 3H), 6.49-6.40 (m, 2H), 3.60 (s, 2H),3.45 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −114.12; ESIMS m/z 279([M+H]⁺).

5-Amino-2-chloro-N-(3-fluorophenyl)benzamide (C88)

Isolated as a white solid (1.18 g, 95%): ¹H NMR (400 MHz, CDCl₃) δ 8.05(s, 1H), 7.63 (dt, J=10.9, 2.2 Hz, 1H), 7.31 (td, J=8.1, 6.2 Hz, 1H),7.26-7.22 (m, 1H), 7.20 (d, J=8.5 Hz, 1H), 7.09 (d, J=3.0 Hz, 1H), 6.86(tdd, J=8.3, 2.5, 1.1 Hz, 1H), 6.71 (dd, J=8.6, 2.9 Hz, 1H), 3.84 (s,2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −111.22; ESIMS m/z 265 ([M+H]⁺).

5-Amino-2-chloro-N-(3-cyanophenyl)benzamide (C89)

Isolated as a white solid (0.89 g, 70%): ¹H NMR (400 MHz, DMSO-d₆) δ10.75 (s, 1H), 8.23-8.14 (m, 1H), 7.95 (td, J=4.7, 2.2 Hz, 1H),7.66-7.50 (m, 2H), 7.15 (d, J=8.6 Hz, 1H), 6.76-6.60 (m, 2H), 5.52 (s,2H); ¹³C NMR (101 MHz, DMSO-d₆) δ 165.98, 147.85, 139.77, 136.41,130.29, 129.99, 127.17, 123.96, 121.98, 118.63, 116.18, 115.03, 113.32,111.60; ESIMS m/z 272 ([M+H]⁺).

5-Amino-2-chloro-N-(2,3-difluorophenyl)benzamide (C90)

Isolated as a white solid (1.11 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 8.38(s, 1H), 8.29-8.20 (m, 1H), 7.22 (d, J=8.6 Hz, 1H), 7.17-7.06 (m, 2H),6.95 (dddd, J=9.9, 8.6, 7.6, 1.5 Hz, 1H), 6.73 (dd, J=8.6, 2.9 Hz, 1H),3.85 (s, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −137.88 (d, J=20.5 Hz), −154.65(d, J=20.4 Hz); ESIMS m/z 283 ([M+H]⁺).

5-Amino-2-chloro-N-(3,4-difluorophenyl)benzamide (C91)

Isolated as a grey solid (1.26 g, 93%): ¹H NMR (400 MHz, CDCl₃) δ 8.03(s, 1H), 7.76 (ddd, J=12.1, 7.2, 2.3 Hz, 1H), 7.23-7.08 (m, 4H), 6.72(dd, J=8.6, 2.9 Hz, 1H), 3.85 (s, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ−135.39 (d, J=21.6 Hz), −141.93 (d, J=21.7 Hz); ESIMS m/z 283 ([M+H]⁺).

5-Amino-2-chloro-N-(2,4,6-trifluorophenyl)benzamide (C92)

Isolated as a light brown solid (1.20 g, 73%): ¹H NMR (400 MHz, DMSO-d₆)δ 10.08 (s, 1H), 7.38-7.27 (m, 2H), 7.14 (d, J=8.6 Hz, 1H), 6.74 (d,J=2.7 Hz, 1H), 6.65 (dd, J=8.6, 2.8 Hz, 1H), 5.52 (s, 2H); ¹⁹F NMR (376MHz, DMSO-d₆) δ −109.56 (t, J=5.5 Hz), −114.48 (d, J=5.5 Hz); ESIMS m/z301 ([M+H]+).

5-Amino-2-chloro-N-(2,6-difluorophenyl)benzamide (C93)

Isolated as a light brown solid (0.93 g, 98%): ¹H NMR (400 MHz, DMSO-d₆)δ 10.09 (s, 1H), 7.40 (tt, J=8.4, 6.3 Hz, 1H), 7.26-7.10 (m, 3H), 6.75(d, J=2.7 Hz, 1H), 6.65 (dd, J=8.6, 2.8 Hz, 1H), 5.51 (s, 2H); ¹⁹F NMR(376 MHz, DMSO-d₆) δ −117.62; ESIMS m/z 283 ([M+H]⁺).

3-Amino-4-chloro-N-(4-fluorophenyl)benzamide (C94)

Isolated as a white solid (0.147 g, 23%): ¹H NMR (400 MHz, DMSO-d₆) δ10.21 (s, 1H), 7.83-7.69 (m, 2H), 7.39-7.27 (m, 2H), 7.23-7.14 (m, 2H),7.10 (dd, J=8.3, 2.1 Hz, 1H), 5.61 (s, 2H); IR (thin film) 3472, 3379,1659 cm⁻¹; ESIMS m/z 265 ([M+H]⁺).

5-Amino-2-chloro-N-(pyridin-4-yl)benzamide (C95)

Isolated as a yellow solid (0.385 g, 89%): ¹H NMR (400 MHz, CD₃OD) δ8.44 (dt, J=5.0, 1.3 Hz, 2H), 7.78-7.71 (m, 2H), 7.17 (dd, J=8.6, 1.2Hz, 1H), 6.83 (dd, J=2.8, 1.1 Hz, 1H), 6.77 (ddd, J=8.6, 2.8, 1.1 Hz,1H); ¹³C NMR (101 MHz, CDCl₃) δ 171.98, 153.55, 153.30, 151.33, 150.57,140.02, 134.02, 121.26, 117.90; ESIMS m/z 248 ([M+H]⁺).

5-Amino-2-chloro-N-(pyridin-3-yl)benzamide (C96)

Isolated as a yellow solid (0.341 g, 80%): ¹H NMR (400 MHz, CD₃OD) δ8.82 (d, J=2.5 Hz, 1H), 8.31 (dt, J=4.9, 1.2 Hz, 1H), 8.23 (ddt, J=8.4,2.6, 1.2 Hz, 1H), 7.45 (dd, J=8.4, 4.9 Hz, 1H), 7.17 (dd, J=8.6, 1.0 Hz,1H), 6.85 (dd, J=2.7, 1.0 Hz, 1H), 6.77 (ddd, J=8.7, 2.8, 1.0 Hz, 1H);¹³C NMR (126 MHz, CD₃OD) δ 167.78, 147.36, 144.18, 140.67, 136.19,135.99, 130.06, 127.82, 123.97, 117.41, 117.22, 114.04; ESIMS m/z 248([M+H]⁺).

3-Amino-N-(4-fluorophenyl)-2-methoxybenzamide (C97)

Isolated as a yellow oil (0.541 g, quant): ¹H NMR (400 MHz, CDCl₃) δ9.61 (s, 1H), 7.69-7.61 (m, 2H), 7.50 (dd, J=7.8, 1.6 Hz, 1H), 7.13-7.02(m, 3H), 6.92 (dd, J=7.8, 1.6 Hz, 1H), 3.93 (s, 2H), 3.87 (s, 3H); ¹⁹FNMR (376 MHz, CDCl₃) δ −118.16; ESIMS m/z 261 ([M+H]⁺).

5-Amino-2-chloro-N-(2-chloropyridin-3-yl)benzamide (C98)

Isolated as a yellow solid (0.269 g, 83%): ¹H NMR (400 MHz, DMSO-d₆) δ10.25 (s, 1H), 8.30 (dd, J=4.7, 1.8 Hz, 1H), 8.09 (d, J=8.1 Hz, 1H),7.49 (dd, J=7.9, 4.7 Hz, 1H), 7.14 (d, J=8.6 Hz, 1H), 6.79 (d, J=2.8 Hz,1H), 6.66 (dd, J=8.6, 2.7 Hz, 1H), 5.51 (s, 2H); ¹³C NMR (101 MHz,DMSO-d₆) δ 165.98, 147.76, 146.42, 145.29, 135.89, 135.82, 131.61,129.99, 123.44, 116.25, 115.23, 113.61; ESIMS m/z 282 ([M+H]⁺).

5-Amino-2-chloro-N-(6-chloropyridin-3-yl)benzamide (C99)

Isolated as a yellow solid (0.560 g, 69%): ¹H NMR (400 MHz, DMSO-d₆) δ10.77 (s, 1H), 8.72 (d, J=2.7 Hz, 1H), 8.19 (dd, J=8.7, 2.7 Hz, 1H),7.52 (d, J=8.7 Hz, 1H), 7.16 (d, J=8.6 Hz, 1H), 6.73 (d, J=2.7 Hz, 1H),6.68 (dd, J=8.6, 2.8 Hz, 1H), 5.52 (s, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ165.95, 147.84, 143.95, 140.56, 136.17, 135.28, 130.02, 129.94, 124.27,116.25, 115.04, 113.36; ESIMS m/z 282 ([M+H]⁺).

5-Amino-2-chloro-N-(6-cyanopyridin-3-yl)benzamide (C100)

Isolated as a yellow solid (0.292 g, 45%): ¹H NMR (400 MHz, DMSO-d₆) δ11.10 (s, 1H), 8.98 (d, J=2.5 Hz, 1H), 8.38 (dd, J=8.6, 2.6 Hz, 1H),8.03 (d, J=8.7 Hz, 1H), 7.17 (d, J=8.6 Hz, 1H), 6.74 (d, J=2.7 Hz, 1H),6.69 (dd, J=8.6, 2.8 Hz, 1H), 5.54 (d, J=9.0 Hz, 2H); ¹³C NMR (101 MHz,DMSO-d₆) δ 166.45, 147.89, 142.08, 138.85, 135.78, 130.11, 129.70,126.37, 126.12, 117.64, 116.48, 114.98, 113.33; ESIMS m/z 273 ([M+H]⁺).

5-Amino-2-chloro-N-(3-fluorophenyl)-N-methylbenzamide (C101)

Isolated as a yellow oil (0.446 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.16(d, J=7.9 Hz, 2H), 7.03-6.77 (m, 4H), 6.47 (s, 2H), 3.61 (s, 2H), 3.47(s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −111.45; ESIMS m/z 279 ([M+H]⁺).

5-Amino-2-chloro-N-(2-fluorophenyl)-N-methylbenzamide (C102)

Isolated as a red-orange oil (0.542 g, quant): ¹H NMR (400 MHz, CDCl₃) δ7.26-7.13 (m, 2H), 7.04-6.94 (m, 2H), 6.91 (d, J=8.6 Hz, 1H), 6.52 (dd,J=2.8, 1.4 Hz, 1H), 6.41 (dd, J=8.6, 2.8 Hz, 1H), 3.59 (s, 2H), 3.42 (d,J=0.6 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −120.54; ESIMS m/z 279([M+H]⁺).

5-Amino-2-chloro-N-(4-cyano-2-methylphenyl)benzamide (C103)

Isolated as a white solid (0.390 g, 86%): ¹H NMR (400 MHz, CDCl₃) δ 8.43(d, J=8.6 Hz, 1H), 8.23 (s, 1H), 7.57 (dd, J=8.5, 2.0 Hz, 1H), 7.50 (d,J=1.9 Hz, 1H), 7.22 (d, J=8.6 Hz, 1H), 7.19 (d, J=2.9 Hz, 1H), 6.75 (dd,J=8.6, 2.9 Hz, 1H), 3.88 (s, 2H), 2.38 (s, 3H); ¹³C NMR (101 MHz, CDCl₃)δ 145.97, 140.12, 134.26, 134.01, 131.35, 131.27, 128.18, 121.64,118.89, 118.76, 118.44, 117.09, 107.72, 17.93; ESIMS m/z 286 ([M+H]⁺).

5-Amino-2-chloro-N-(4-fluoro-2-methylphenyl)benzamide (C104)

Isolated as a red solid (0.430 g, 95%): ¹H NMR (400 MHz, DMSO-d₆) δ 9.84(s, 1H), 7.34 (dd, J=8.8, 5.7 Hz, 1H), 7.12 (dd, J=9.0, 2.4 Hz, 2H),7.04 (td, J=8.6, 3.0 Hz, 1H), 6.74 (d, J=2.7 Hz, 1H), 6.63 (dd, J=8.6,2.8 Hz, 1H), 5.46 (s, 2H), 2.27 (s, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ−117.12; ESIMS m/z 279 ([M+H]⁺).

6-Amino-N-(4-fluorophenyl)picolinamide (C105)

Isolated as a green film (0.072 g, 15%): ¹H NMR (400 MHz, CDCl₃) δ 9.82(s, 1H), 7.70 (dd, J=7.2, 4.8 Hz, 2H), 7.67-7.52 (m, 2H), 7.05 (t, J=8.3Hz, 2H), 6.67 (d, J=7.6 Hz, 1H), 4.63 (s, 2H); IR (thin film) 3333,1671, 1608 cm⁻¹; ESIMS m/z 232 ([M+H]⁺).

3-Amino-N-(4-fluorophenyl)-4-methylbenzamide (C106)

Isolated as a faint yellow solid (0.102 g, 15%): ¹H NMR (400 MHz,DMSO-d₆) δ 10.05 (s, 1H), 7.82-7.71 (m, 2H), 7.20-7.11 (m, 3H),7.09-7.01 (m, 2H), 5.07 (s, 2H), 2.11 (s, 3H); IR (thin film) 3366,2924, 1655 cm⁻¹; ESIMS m/z 245 ([M+H]⁺).

5-Amino-N-(4-fluorophenyl)-2-(trifluoromethoxy)benzamide (C107)

Isolated as a white solid (0.448 g, 81%): mp 115-117° C.; ¹H NMR (400MHz, DMSO-d₆) δ 10.39 (s, 1H), 7.76-7.64 (m, 2H), 7.23-7.15 (m, 2H),7.10 (d, J=8.9 Hz, 1H), 6.76 (d, J=2.8 Hz, 1H), 6.70 (dd, J=8.8, 2.8 Hz,1H), 5.57 (s, 2H); ESIMS m/z 315 ([M+H]⁺).

3-Amino-5-chloro-N-(4-fluorophenyl)benzamide (C108)

Isolated as a light brown solid (0.497 g, 81%): mp 133-136° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 10.23 (d, J=8.3 Hz, 1H), 7.82-7.68 (m, 2H),7.25-7.12 (m, 2H), 7.10-7.00 (m, 2H), 6.76 (t, J=2.0 Hz, 1H), 5.69 (s,2H); ESIMS m/z 265 ([M]⁺).

5-Amino-2-chloro-N-(2-chlorophenyl)benzamide (C109)

Isolated as a red oil (0.391 g, 69%): ¹H NMR (400 MHz, CDCl₃) δ8.60-8.53 (m, 2H), 7.41 (dd, J=8.0, 1.5 Hz, 1H), 7.33 (td, J=8.0, 1.6Hz, 1H), 7.22 (d, J=8.5 Hz, 1H), 7.13 (dd, J=6.1, 2.2 Hz, 1H), 7.09 (td,J=7.8, 1.6 Hz, 1H), 6.73 (dd, J=8.6, 2.9 Hz, 1H), 3.85 (s, 2H); ¹³C NMR(101 MHz, CDCl₃) δ 145.70, 134.98, 131.82, 131.30, 129.17, 127.77,126.29, 125.00, 122.04, 121.82, 118.45, 116.57; ESIMS m/z 281 ([M+H]⁺).

5-Amino-2-chloro-N-(2-isopropylphenyl)benzamide (C110)

Isolated as a red oil (0.461 g, 81%): ¹H NMR (400 MHz, CDCl₃) δ 7.92 (s,1H), 7.85 (dd, J=7.5, 1.9 Hz, 1H), 7.34 (dd, J=7.2, 2.2 Hz, 1H),7.29-7.18 (m, 3H), 7.17 (d, J=2.9 Hz, 1H), 6.71 (dd, J=8.6, 2.9 Hz, 1H),3.84 (s, 2H), 3.16 (hept, J=6.9 Hz, 1H), 1.27 (d, J=6.8 Hz, 6H); ¹³C NMR(101 MHz, CDCl₃) δ 162.79, 145.76, 140.95, 133.86, 131.14, 126.46,126.40, 125.71, 124.85, 118.20, 116.87, 28.04, 23.22; ESIMS m/z 289([M+H]⁺).

5-Amino-2-chloro-N-(2-ethyl-6-methylphenyl)benzamide (C111)

Isolated as a red oil (0.512 g, 74%): ¹H NMR (400 MHz, CDCl₃) δ 7.57 (s,1H), 7.25-7.10 (m, 5H), 6.71 (dd, J=8.6, 2.9 Hz, 1H), 3.83 (s, 2H), 2.70(q, J=7.6 Hz, 2H), 2.34 (s, 3H), 1.22 (t, J=7.6 Hz, 3H); ¹³C NMR (101MHz, CDCl₃) δ 161.01, 145.71, 144.07, 141.41, 136.23, 135.17, 131.13,128.40, 127.96, 126.51, 118.95, 118.13, 116.80, 25.18, 18.86, 14.74;ESIMS m/z 289 ([M+H]⁺).

5-Amino-2-chloro-N-(3-chlorophenyl)benzamide (C112)

Isolated as an orange solid (0.470 g, 62%): ¹H NMR (400 MHz, CDCl₃) δ8.02 (d, J=8.1 Hz, 1H), 7.76 (dt, J=3.8, 2.1 Hz, 1H), 7.53-7.43 (m, 1H),7.34-7.28 (m, 1H), 7.19 (d, J=8.5 Hz, 1H), 7.14 (ddd, J=8.0, 2.0, 1.0Hz, 1H), 7.07 (d, J=2.9 Hz, 1H), 6.71 (dd, J=8.6, 2.9 Hz, 1H), 3.84 (s,2H); ESIMS m/z 281 ([M+H]⁺).

5-Amino-2-chloro-N-(2,4-difluorophenyl)-N-methylbenzamide (C113)

Isolated as a yellow foam (0.495 g, 91%): ¹H NMR (300 MHz, CDCl₃) δ 6.93(d, J=8.6 Hz, 1H), 6.82-6.64 (m, 3H), 6.52 (d, J=2.6 Hz, 1H), 6.44 (dd,J=8.6, 2.8 Hz, 1H), 3.62 (s, 2H), 3.39 (s, 3H); IR (thin film) 3355,1645, 1510 cm⁻¹; ESIMS m/z 297 ([M+H]⁺).

5-Amino-2-chloro-4-fluoro-N-(4-fluorophenyl)benzamide (C114)

Isolated as a yellow foam (0.442 g, 95%): ¹H NMR (300 MHz, DMSO-d₆) δ10.44 (s, 1H), 7.87-7.63 (m, 2H), 7.28 (d, J=11.2 Hz, 1H), 7.24-7.12 (m,2H), 6.92 (d, J=9.4 Hz, 1H), 5.56 (s, 2H); ESIMS m/z 283 ([M+H]⁺).

5-Amino-2-chloro-N-(5-fluoropyridin-2-yl)benzamide (C115)

Isolated as a yellow solid (0.073 g, 90%): ¹H NMR (400 MHz, DMSO-d₆) δ10.96 (s, 1H), 8.35 (d, J=3.1 Hz, 1H), 8.26-8.15 (m, 1H), 7.79 (td,J=8.7, 3.0 Hz, 1H), 7.18 (d, J=8.8 Hz, 1H), 6.89-6.73 (m, 2H), 5.44 (s,2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −132.77; ESIMS m/z 266 ([M+H]⁺).

5-(5-Amino-2-chlorobenzamido)-N-methylpicolinamide (C116)

Isolated as a yellow foam (0.187 g, quant): ¹H NMR (400 MHz, DMSO-d₆) δ10.86 (s, 1H), 8.92 (dd, J=5.0, 2.4 Hz, 1H), 8.66 (d, J=5.0 Hz, 1H),8.30 (dt, J=8.6, 2.3 Hz, 1H), 8.03 (dd, J=8.6, 2.5 Hz, 1H), 7.16 (d,J=8.6 Hz, 1H), 6.74 (d, J=2.7 Hz, 1H), 6.68 (dd, J=8.6, 2.7 Hz, 1H),5.52 (s, 2H), 2.81 (d, J=4.8 Hz, 3H); ESIMS m/z 305 ([M+H]⁺).

5-Amino-2-chloro-N-(pyridin-2-yl)benzamide (C117)

Isolated as a yellow foam (0.152 g, 49%): ¹H NMR (400 MHz, DMSO-d₆) δ11.25 (s, 1H), 8.74 (d, J=2.7 Hz, 1H), 8.46 (d, J=2.8 Hz, 1H), 8.41-8.35(m, 1H), 8.32 (dd, J=8.9, 2.8 Hz, 1H), 8.25 (dd, J=8.8, 2.7 Hz, 1H),8.20 (d, J=8.4 Hz, 1H), 7.92-7.78 (m, 3H), 7.21 (ddd, J=7.4, 4.9, 1.0Hz, 1H); EIMS m/z 248 ([M+H]⁺).

N-Allyl-5-amino-2-chloro-N-(4-fluorophenyl)benzamide (C118)

Isolated as an orange solid (0.269 g, 60%): ESIMS m/z 305 ([M+H]⁺).

Example 24: Preparation of 5-amino-2-fluoro-N-(4-fluorophenyl)benzamide(C119)

To a solution of 2-fluoro-N-(4-fluorophenyl)-5-nitrobenzamide (C183)(1.06 g, 3.81 mmol) in ethyl acetate (15 mL) under a nitrogen blanketwas added palladium on carbon (0.120 g, 0.0560 mmol). The reaction flaskwas placed on a Parr shaker at room temperature under hydrogen (45 psi)for 16 hours. The reaction was filtered through Celite®, washed withethyl acetate, and concentrated to provide the title product as a whitesolid (0.955 g, quant)¹H NMR (400 MHz, CDCl₃) δ 8.46 (d, J=17.1 Hz, 1H),7.65-7.58 (m, 2H), 7.42 (dd, J=6.5, 3.1 Hz, 1H), 7.11-7.03 (m, 2H), 6.98(dd, J=11.8, 8.8 Hz, 1H), 6.78 (ddd, J=8.7, 4.1, 3.1 Hz, 1H), 3.74 (s,2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −117.55, −126.58; EIMS m/z 249 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 24:

3-Amino-2-fluoro-N-(4-fluorophenyl)benzamide (C120)

Isolated as a white solid (1.05 g, 96%): ¹H NMR (400 MHz, CDCl₃) δ 8.28(d, J=13.9 Hz, 1H), 7.66-7.57 (m, 2H), 7.43 (ddd, J=7.8, 7.0, 1.7 Hz,1H), 7.12-7.03 (m, 3H), 6.95 (ddd, J=8.7, 7.9, 1.7 Hz, 1H), 3.87 (s,2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −117.54, −136.71; EIMS m/z 249 ([M+H]⁺).

5-Amino-2-fluoro-N-(4-fluorophenyl)-N-methylbenzamide (C121)

Isolated as a white foam (0.618 g, 98%): ¹H NMR (300 MHz, CDCl₃) δ7.12-7.01 (m, 2H), 6.96-6.83 (m, 2H), 6.67-6.44 (m, 3H), 3.54 (br s,2H), 3.44 (s, 3H); IR (thin film) 3351, 2922, 1638, 1509 cm⁻¹; ESIMS m/z263 ([M+H]⁺).

5-Amino-2-fluoro-N-(3-fluorophenyl)-N-methylbenzamide (C122)

Isolated as a white foam (0.595 g, quant): EIMS m/z 263 ([M+H]⁺).

3-Amino-2-fluoro-N-(4-fluorophenyl)-N-methylbenzamide (C123)

Isolated as a green solid (0.595 g, quant): ¹H NMR (300 MHz, CDCl₃) δ7.05 (s, 2H), 6.89 (t, J=8.3 Hz, 2H), 6.77 (t, J=7.7 Hz, 1H), 6.59 (dt,J=13.9, 7.6 Hz, 2H), 3.62 (s, 2H), 3.45 (s, 3H); EIMS m/z 263 ([M+H]⁺).

5-Amino-2,4-difluoro-N-(4-fluorophenyl)benzamide (C124)

Isolated as a white foam (0.436 g, 87%): ¹H NMR (300 MHz, CDCl₃) δ 8.37(d, J=16.6 Hz, 1H), 7.66-7.53 (m, 3H), 7.11-7.02 (m, 2H), 6.89 (dd,J=11.6, 10.2 Hz, 1H), 3.79 (s, 2H); EIMS m/z 267 ([M+H]⁺).

5-Amino-N-(2,4-difluorophenyl)-2-fluorobenzamide (C125)

Isolated as a white solid (0.90 g, quant): ¹H NMR (400 MHz, CDCl₃) δ8.71 (d, J=17.8 Hz, 1H), 8.43 (td, J=9.1, 6.0 Hz, 1H), 7.42 (dd, J=6.4,3.1 Hz, 1H), 6.99 (dd, J=11.7, 8.7 Hz, 1H), 6.96-6.86 (m, 2H), 6.80(ddd, J=8.7, 4.1, 3.1 Hz, 1H), 3.82 (s, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ−114.82 (d, J=4.6 Hz), −125.88 (d, J=4.6 Hz), −126.34 (d, J=1.4 Hz);EIMS m/z 267 ([M+H]⁺).

5-Amino-N-(2,4-difluorophenyl)-2-fluoro-N-methylbenzamide (C126)

Isolated as a brown oil (0.54 g, 57%): ¹H NMR (400 MHz, DMSO-d₆) δ7.40-7.21 (m, 2H), 7.00 (t, J=8.6 Hz, 1H), 6.63 (t, J=9.1 Hz, 1H),6.50-6.37 (m, 2H), 5.01 (s, 2H), 3.25 (s, 3H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −109.77 (d, J=7.6 Hz), −116.51 (t, J=7.1 Hz), −131.34 (d,J=6.2 Hz); EIMS m/z 281 ([M+H]⁺).

5-Amino-2-fluoro-N-methyl-N-phenylbenzamide (C127)

Isolated as a white solid (0.92 g, 71%): ¹H NMR (400 MHz, DMSO-d₆) δ7.40-7.05 (m, 5H), 6.63 (s, 1H), 6.43 (s, 2H), 4.97 (s, 2H), 3.32 (s,3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −131.23; EIMS m/z 245 ([M+H]⁺).

3-Amino-2-fluoro-N-methyl-N-phenylbenzamide (C128)

Isolated as a white solid (1.07 g, 87%): ¹H NMR (400 MHz, DMSO-d₆) δ7.41-7.00 (m, 5H), 6.64 (d, J=39.8 Hz, 2H), 6.35 (s, 1H), 5.07 (s, 2H),3.32 (s, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −137.79; EIMS m/z 245([M+H]⁺).

5-Amino-N-(4-cyano-2-fluorophenyl)-2-fluorobenzamide (C129)

Isolated as a yellow solid (0.447 g, 95%): ¹H NMR (400 MHz, DMSO-d₆) δ10.32-10.14 (m, 1H), 8.17 (t, J=8.1 Hz, 1H), 7.95 (dd, J=10.8, 1.8 Hz,1H), 7.72 (dt, J=8.4, 1.2 Hz, 1H), 7.01 (dd, J=10.5, 8.8 Hz, 1H), 6.89(dd, J=6.0, 2.9 Hz, 1H), 6.73 (ddd, J=8.8, 4.2, 2.9 Hz, 1H), 5.25 (s,2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −120.96, −130.61; EIMS m/z 274([M+H]⁺).

5-Amino-2-chloro-N-ethyl-N-(4-fluorophenyl)benzamide (C130)

Isolated as a white solid (0.201 g, 98%): EIMS m/z 293 ([M+H]⁺).

5-Amino-2-chloro-N-(4-fluorophenyl)-N-(2,2,2-trifluoroethyl)benzamide(C131)

Isolated as a white solid (0.125 g, 97%): EIMS m/z 347 ([M+H]⁺).

5-Amino-2-chloro-N-(4-fluorophenyl)-N-propylbenzamide (C132)

Isolated as a white solid (0.267 g, 99%): EIMS m/z 307 ([M+H]⁺).

5-Amino-N-(4-cyano-2-fluorophenyl)-2-fluoro-N-methylbenzamide (C133)

Isolated as an orange solid (0.120 g, 22%): ¹H NMR (400 MHz, CDCl₃) δ7.45-7.17 (m, 4H), 6.70 (dd, J=5.4, 2.8 Hz, 1H), 6.68-6.52 (m, 1H), 3.63(s, 2H), 3.40 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −116.04, −126.81; EIMSm/z 288 ([M+H]⁺).

5-Amino-2-chloro-N-(4-cyano-2-fluorophenyl)-N-methylbenzamide (C134)

Isolated as a red-orange solid (0.248 g, 33%): EIMS m/z 304 ([M+H]⁺).

Example 25: Preparation of6-Amino-3-chloro-N-(4-fluorophenyl)picolinamide (C135)

Step 1. 6-[bis(tert-butoxycarbonyl)amino]-3-chloro-pyridine-2-carboxylicacid (C136) and6-(tert-butoxycarbonylamino)-3-chloro-pyridine-2-carboxylic acid (C137)

To a solution of methyl6-[bis(tert-butoxycarbonyl)amino]-3-chloro-pyridine-2-carboxylate (C211)(0.500 g, 1.29 mmol) in tetrahydrofuran (6.5 mL) and water (1.4 mL) wasadded lithium hydroxide (0.0930 g, 3.88 mmol). After 3 hours, thereaction was acidified with hydrochloric acid (0.5 N), and the reactionmixture was extracted with ethyl acetate. The combined organic phaseswere washed with water, dried over magnesium sulfate, and concentratedto provide a 3:1 mixture of (C136) and (C137) (0.308 g).

Step 2. tert-butylN-tert-butoxycarbonyl-N-[5-chloro-6-[(4-fluorophenyl)carbamoyl]-2-pyridyl]carbamate(C138) and tert-butylN-[5-chloro-6-[(4-fluorophenyl)carbamoyl]-2-pyridyl]carbamate (C139)

6-[Bis(tert-butoxycarbonyl)amino]-3-chloro-pyridine-2-carboxylic acid(C136) and 6-(tert-butoxycarbonylamino)-3-chloro-pyridine-2-carboxylicacid (C137) (0.308 g) was dissolved in 1,2-dichloroethane (3.5 mL) and4-dimethylaminopyridine (0.165 g, 1.35 mmol), 4-fluoroaniline (0.118 mL,1.24 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimidehydrochloride (0.298 g, 1.56 mmol) were added at room temperature. Thereaction was stirred at room temperature overnight. The reaction mixturewas diluted with dichloromethane and washed with saturated aqueoussodium bicarbonate followed by hydrochloric acid (1 N) to provide a 3:1mixture of (C138) and (C139) (0.537 g).

Step 3. 6-amino-3-chloro-N-(4-fluorophenyl)picolinamide (C135)

The mixture of (C138) and (C139) (0.537 g) were dissolved indichloromethane (2.4 mL), and trifluoroacetic acid (2.4 mL) was added.After 30 minutes, the reaction was poured into a separatory funnel andcarefully quenched with saturated aqueous sodium bicarbonate. Themixture was extracted with dichloromethane. The combined organic phaseswere dried over magnesium sulfate, and concentrated to provide the titlecompound as a white solid (0.223 g, 0.797 mmol): ¹H NMR (400 MHz,DMSO-d₆) δ 10.49 (s, 1H), 7.79-7.66 (m, 2H), 7.54 (d, J=8.8 Hz, 1H),7.24-7.14 (m, 2H), 6.58 (d, J=8.8 Hz, 1H), 6.44 (s, 2H); IR (thin film)3476, 3339, 1685 cm⁻¹; EIMS m/z 266 ([M]⁺).

Example 26: Preparation of5-amino-2-chloro-N-(4-fluorophenyl)-N-methylbenzothioamide (C140)

To a solution of 5-amino-2-chloro-N-(4-fluorophenyl)benzamide (C69)(0.300 g, 1.13 mmol) in tetrahydrofuran (4 mL) was added1,1,1,3,3,3-hexamethyldisiloxane (1.21 mL, 5.67 mmol) followed byphosphorus pentasulfide (0.529 g, 2.38 mmol) in one portion. Thereaction was warmed to 60° C. for 3 hours, cooled to room temperature,and filtered over a pad of Celite®. The filtrates were partitionedbetween ethyl acetate and water. Brine was added until a phase cut wasachieved. The phases were separated, and the organic layer adsorbed ontoseveral scoops of Celite®. Purification by flash column chromatographyprovided the title compound as a yellow solid (0.108 g, 34%): ESIMS m/z295 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 26:

5-Amino-2-chloro-N-(4-fluorophenyl)benzothioamide (C141)

Isolated as a yellow solid (0.108 g, 34%): ESIMS m/z 281 ([M+H]⁺).

Example 27: Preparation of 5-amino-2-cyano-N-(4-fluorophenyl)benzamide(C142)

To a solution of 5-amino-2-bromo-N-(4-fluorophenyl)benzamide (C79)(0.460 g, 1.49 mmol) in N,N-dimethylformamide (4.25 mL) was addedcopper(I) cyanide (0.666 g, 7.44 mmol). The reaction was degassed undervacuum, backfilled with nitrogen, capped in a 25-mL vial, and heated at160° C. for 20 minutes in a Biotage Initiator® microwave reactor withexternal IR-sensor temperature monitoring from the side of the vessel.The reaction was diluted with ethyl acetate while stirring vigorouslyand filtered through Celite® washing with ethyl acetate. The filtratewas washed with brine. The organic phase was dried over magnesiumsulfate, filtered, and concentrated to provide the title compound as ayellow solid (0.106 g, 24%): ¹H NMR (400 MHz, DMSO-d₆) δ 9.53 (s, 1H),7.85 (d, J=8.0 Hz, 1H), 7.48-7.42 (m, 2H), 7.37-7.29 (m, 2H), 6.94 (s,1H), 6.89 (d, J=9.0 Hz, 1H), 6.21 (s, 2H); ESIMS m/z 256 ([M+H]⁺).

Example 28: Preparation of 2-chloro-N-(4-fluorophenyl)-5-nitrobenzamide(C143)

2-Chloro-5-nitrobenzoic acid (0.250 g, 1.24 mmol) and4-dimethylaminopyridine (0.197 g, 1.61 mmol) were sequentially added toa stirred mixture of 4-fluoroaniline (0.141 ml, 1.49 mmol) and1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.357 g,1.86 mmol) in 1,2-dichloroethane (12.4 mL) at room temperature. Thereaction was stirred at room temperature for 20 hours. The reactionmixture was diluted with dichloromethane and washed with saturatedaqueous sodium bicarbonate followed by hydrochloric acid (1 N) toprovide the title compound as a light brown solid (0.188 g, 49%): ¹H NMR(400 MHz, CDCl₃) δ 8.59 (d, J=2.7 Hz, 1H), 8.26 (dd, J=8.8, 2.8 Hz, 1H),7.90 (s, 1H), 7.66 (d, J=8.8 Hz, 1H), 7.64-7.57 (m, 2H), 7.15-7.05 (m,2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −116.03; ESIMS m/z 295 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 28:

N-(4-Fluorophenyl)-5-nitro-2-(trifluoromethyl)benzamide (C144)

Isolated as a light brown solid (0.299 g, 41%): ¹H NMR (400 MHz, CDCl₃)δ 8.52 (d, J=2.1 Hz, 1H), 8.44 (dd, J=8.7, 1.4 Hz, 1H), 7.99 (d, J=8.6Hz, 1H), 7.61-7.52 (m, 2H), 7.47 (s, 1H), 7.15-7.06 (m, 2H); EIMS m/z328 ([M]⁺).

N-(4-Fluorophenyl)-2-iodo-5-nitrobenzamide (C145)

Isolated as a brown solid (0.258 g, 37%): ¹H NMR (400 MHz, DMSO-d₆) δ10.68 (s, 1H), 8.29 (d, J=2.7 Hz, 1H), 8.26 (d, J=8.6 Hz, 1H), 8.03 (dd,J=8.6, 2.7 Hz, 1H), 7.77-7.67 (m, 2H), 7.30-7.19 (m, 2H); IR (thin film)3219, 3069, 1651 cm⁻¹; ESIMS m/z 387 ([M+H]⁺).

2-Chloro-N-(4-cyanophenyl)-5-nitrobenzamide (C146)

Isolated as a yellow solid (0.252 g, 30%): ¹H NMR (400 MHz, DMSO-d₆) δ11.15 (s, 1H), 8.55 (d, J=2.7 Hz, 1H), 8.37 (dd, J=8.8, 2.8 Hz, 1H),7.98-7.80 (m, 5H); IR (thin film) 3275, 3100, 2222, 1667 cm⁻¹; ESIMS m/z303 ([M+H]⁺).

2-Chloro-5-nitro-N-(4-(trifluoromethyl)phenyl)benzamide (C147)

Isolated as a yellow solid (0.316 g, 35%): ¹H NMR (400 MHz, CDCl₃) δ8.63 (d, J=2.7 Hz, 1H), 8.30 (dd, J=8.8, 2.7 Hz, 1H), 8.00 (s, 1H), 7.79(d, J=8.5 Hz, 2H), 7.72-7.63 (m, 3H); IR (thin film) 3255, 3078, 1663cm⁻¹; ESIMS m/z 346 ([M+H]⁺).

2-Chloro-N-(4-chlorophenyl)-5-nitrobenzamide (C148)

Isolated as a yellow solid (0.339 g, 42%): ¹H NMR (400 MHz, CDCl₃) δ8.62 (d, J=2.7 Hz, 1H), 8.28 (dd, J=8.8, 2.7 Hz, 1H), 7.84 (s, 1H), 7.67(d, J=8.8 Hz, 1H), 7.60 (d, J=8.8 Hz, 2H), 7.38 (d, J=8.8 Hz, 2H); IR(thin film) 3246, 3105, 1657 cm⁻¹; ESIMS m/z 312 ([M+H]⁺).

2-Chloro-N-(2-chloro-4-fluorophenyl)-5-nitrobenzamide (C149)

Isolated as a yellow solid (0.135 g, 13%): ¹H NMR (400 MHz, CDCl₃) δ8.70 (d, J=2.7 Hz, 1H), 8.49 (dd, J=9.2, 5.6 Hz, 1H), 8.37 (s, 1H), 8.31(dd, J=8.8, 2.7 Hz, 1H), 7.70 (d, J=8.8 Hz, 1H), 7.22 (dd, J=7.9, 2.9Hz, 1H), 7.11 (ddd, J=9.2, 7.9, 2.9 Hz, 1H); IR (thin film) 3237, 3104,1660 cm⁻¹; ESIMS m/z 330 ([M+H]⁺).

2-Chloro-5-nitro-N-(o-tolyl)benzamide (C150)

Isolated as a light red solid (0.221 g, 28%): ¹H NMR (400 MHz, CDCl₃) δ8.68 (d, J=2.7 Hz, 1H), 8.28 (dd, J=8.8, 2.7 Hz, 1H), 7.94 (d, J=8.0 Hz,1H), 7.74 (s, 1H), 7.68 (d, J=8.8 Hz, 1H), 7.33-7.26 (m, 2H), 7.18 (t,J=7.0 Hz, 1H), 2.36 (s, 3H); IR (thin film) 3239, 3103, 1656 cm⁻¹; ESIMSm/z 290 ([M−H]⁻).

N-(4-Fluorophenyl)-2-methyl-5-nitrobenzamide (C151)

Isolated as a light brown solid (0.504 g, 63%): ¹H NMR (400 MHz, CDCl₃)δ 8.36 (s, 1H), 8.23 (d, J=8.4 Hz, 1H), 7.67-7.56 (m, 2H), 7.53 (s, 1H),7.47 (d, J=8.5 Hz, 1H), 7.10 (t, J=8.2 Hz, 2H), 2.62 (s, 3H); IR (thinfilm) 3264, 3074, 1648 cm⁻¹; ESIMS m/z 275 ([M+H]⁺).

2-Bromo-N-(4-fluorophenyl)-5-nitrobenzamide (C152)

Isolated as a light brown solid (0.370 g, 51%): ¹H NMR (400 MHz, CDCl₃)δ 8.48 (d, J=2.6 Hz, 1H), 8.17 (dd, J=8.8, 2.7 Hz, 1H), 7.86 (d, J=8.8Hz, 1H), 7.66 (s, 1H), 7.64-7.56 (m, 2H), 7.15-7.06 (m, 2H); IR (thinfilm) 3241, 3097, 1657 cm⁻¹; ESIMS m/z 340 ([M+H]⁺).

N-(4-Fluorophenyl)-5-nitro-2-(1H-1,2,4-triazol-1-yl)benzamide (C153)

Isolated as a brown solid (0.367 g, 47%): ¹H NMR (400 MHz, CDCl₃) δ 8.69(d, J=2.5 Hz, 1H), 8.59 (s, 1H), 8.49 (dd, J=8.7, 2.6 Hz, 1H), 8.19 (s,1H), 7.90 (s, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.50-7.42 (m, 2H), 7.10-7.03(m, 2H); IR (thin film) 3135, 3013, 1673 cm⁻¹; ESIMS m/z 328 ([M+H]⁺).

N-(4-Fluorophenyl)-4-nitropicolinamide (C154)

Isolated as a yellow solid (0.602 g, 74%): ¹H NMR (400 MHz, CDCl₃) δ9.84 (s, 1H), 8.99 (dd, J=2.2, 0.6 Hz, 1H), 8.94 (dd, J=5.3, 0.6 Hz,1H), 8.24 (dd, J=5.3, 2.2 Hz, 1H), 7.80-7.70 (m, 2H), 7.16-7.07 (m, 2H);IR (thin film) 3309, 3076, 1680 cm⁻¹; ESIMS m/z 262 ([M+H]⁺).

2-Chloro-N-(4-fluorophenyl)-3-nitrobenzamide (C155)

Isolated as a yellow solid (0.544 g, 71%): ¹H NMR (400 MHz, CDCl₃) δ7.87 (ddd, J=12.8, 7.9, 1.6 Hz, 2H), 7.65 (s, 1H), 7.62-7.57 (m, 2H),7.54 (t, J=7.9 Hz, 1H), 7.14-7.06 (m, 2H); IR (thin film) 3263, 3079,1654 cm⁻¹; ESIMS m/z 296 ([M+H]⁺).

N-(4-Fluorophenyl)-2-methoxy-5-nitrobenzamide (C156)

Isolated as a light brown solid (0.624 g, 81%): ¹H NMR (400 MHz, CDCl₃)δ 9.46 (s, 1H), 9.15 (d, J=2.9 Hz, 1H), 8.38 (dd, J=9.1, 3.0 Hz, 1H),7.66-7.58 (m, 2H), 7.16 (d, J=9.1 Hz, 1H), 7.11-7.04 (m, 2H), 4.20 (s,3H); IR (thin film) 3350, 2082, 1658 cm⁻¹; ESIMS m/z 291 ([M+H]⁺).

2-Chloro-5-nitro-N-phenylbenzamide (C157)

Isolated as a white solid (1.51 g, 73%): ¹H NMR (400 MHz, CDCl₃) δ 8.61(d, J=2.7 Hz, 1H), 8.26 (dd, J=8.8, 2.7 Hz, 1H), 7.85 (s, 1H), 7.70-7.59(m, 3H), 7.46-7.36 (m, 2H), 7.25-7.18 (m, 1H); ¹³C NMR (101 MHz, CDCl₃)δ 162.10, 137.49, 136.87, 136.54, 131.63, 129.30, 126.00, 125.55,125.37, 120.33, 99.98; ESIMS m/z 277 ([M+H]⁺).

2-Chloro-N-(2-fluorophenyl)-5-nitrobenzamide (C158)

Isolated as a white solid (1.38 g, 63%): ¹H NMR (400 MHz, CDCl₃) δ 8.68(d, J=2.7 Hz, 1H), 8.50-8.40 (m, 1H), 8.29 (dd, J=8.8, 2.8 Hz, 1H), 8.19(s, 1H), 7.68 (d, J=8.8 Hz, 1H), 7.26-7.20 (m, 1H), 7.20-7.12 (m, 2H);¹⁹F NMR (376 MHz, CDCl₃) δ −130.45; ESIMS m/z 295 ([M+H]⁺).

2-Chloro-N-(2,4-difluorophenyl)-5-nitrobenzamide (C159)

Isolated as a light purple solid (1.48 g, 64%): ¹H NMR (400 MHz, CDCl₃)δ 8.68 (d, J=2.7 Hz, 1H), 8.40 (td, J=9.1, 6.7 Hz, 1H), 8.30 (dd, J=8.8,2.7 Hz, 1H), 8.09 (s, 1H), 7.69 (d, J=8.8 Hz, 1H), 7.04-6.89 (m, 2H);¹⁹F NMR (376 MHz, CDCl₃) δ −113.04 (d, J=5.0 Hz), −125.45 (d, J=5.1 Hz);ESIMS m/z 313 ([M+H]⁺).

2-Chloro-N-(4-fluorophenyl)-N-methyl-5-nitrobenzamide (C160)

Isolated as a green solid (1.80 g, 78%): ¹H NMR (400 MHz, CDCl₃) δ8.04-7.97 (m, 2H), 7.40 (dd, J=8.5, 0.7 Hz, 1H), 7.19-7.11 (m, 2H),6.96-6.88 (m, 2H), 3.50 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −112.30;ESIMS m/z 309 ([M+H]⁺).

2-Chloro-N-(3-fluorophenyl)-5-nitrobenzamide (C161)

Isolated as a white solid (1.38 g, 63%): ¹H NMR (400 MHz, CDCl₃) δ 8.62(d, J=2.8 Hz, 1H), 8.28 (dd, J=8.8, 2.7 Hz, 1H), 7.90 (s, 1H), 7.67 (d,J=8.8 Hz, 1H), 7.61 (dt, J=10.5, 2.3 Hz, 1H), 7.36 (td, J=8.2, 6.2 Hz,1H), 7.30-7.27 (m, 1H), 6.93 (tdd, J=8.2, 2.5, 1.0 Hz, 1H); ¹⁹F NMR (376MHz, CDCl₃) δ −110.61; ESIMS m/z 295 ([M+H]⁺).

2-Chloro-N-(3-cyanophenyl)-5-nitrobenzamide (C162)

Isolated as a light solid (1.41 g, 63%): ESIMS m/z 302 ([M+H]⁺).

2-Chloro-N-(2,3-difluorophenyl)-5-nitrobenzamide (C163)

Isolated as a white solid (1.24 g, 53%): ¹H NMR (400 MHz, CDCl₃) δ 8.69(d, J=2.8 Hz, 1H), 8.31 (dd, J=8.8, 2.7 Hz, 1H), 8.23 (t, J=7.3 Hz, 2H),7.70 (d, J=8.8 Hz, 1H), 7.22-7.11 (m, 1H), 7.09-6.96 (m, 1H); ¹⁹F NMR(376 MHz, CDCl₃) δ −137.23 (d, J=20.2 Hz), −154.19 (d, J=20.3 Hz); ESIMSm/z 313 ([M+H]⁺).

2-Chloro-N-(3,4-difluorophenyl)-5-nitrobenzamide (C164)

Isolated as a dark colored solid (1.50 g, 65%): ¹H NM (400 MHz, DMSO-d₆)δ 10.95 (s, 1H), 8.51 (d, J=2.8 Hz, 1H), 8.36 (dd, J=8.8, 2.8 Hz, 1H),7.91 (d, J=8.9 Hz, 1H), 7.89-7.83 (m, 1H), 7.54-7.37 (m, 2H); ¹⁹F NMR(376 MHz, DMSO-d₆) δ −136.87 (d, J=23.1 Hz), −143.43 (d, J=23.0 Hz);ESIMS m/z 313 ([M+H]⁺).

2-Chloro-5-nitro-N-(2,4,6-trifluorophenyl)benzamide (C165)

Isolated as a white solid (1.80 g, 73%): ¹H NMR (400 MHz, DMSO-d₆) δ10.59 (s, 1H), 8.43-8.30 (m, 2H), 7.93 (d, J=8.7 Hz, 1H), 7.44-7.30 (m,2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −108.89 (d, J=5.8 Hz), −114.25 (d,J=5.7 Hz); ESIMS m/z 331 ([M+H]⁺).

2-Chloro-N-(2,6-difluorophenyl)-5-nitrobenzamide (C166)

Isolated as a white solid (1.06 g, 46%): ¹H NMR (400 MHz, DMSO-d₆) δ10.61 (s, 1H), 8.51-8.21 (m, 2H), 7.93 (d, J=8.7 Hz, 1H), 7.60-7.36 (m,1H), 7.25 (t, J=8.2 Hz, 2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −117.43; ESIMSm/z 313 ([M+H]⁺).

4-Chloro-N-(4-fluorophenyl)-3-nitrobenzamide (C167)

Isolated as a yellow solid (0.679 g, 88%): ¹H NMR (400 MHz, CDCl₃) δ8.36 (d, J=2.1 Hz, 1H), 8.04 (dd, J=8.4, 2.1 Hz, 1H), 7.95 (s, 1H), 7.69(d, J=8.4 Hz, 1H), 7.62-7.54 (m, 2H), 7.13-7.04 (m, 2H); IR (thin film)3342, 3075, 1651 cm⁻¹; ESIMS m/z 295 ([M+H]⁺).

N-(4-Fluorophenyl)-2-methoxy-3-nitrobenzamide (C168)

Isolated as a yellow solid (0.600 g, 65%): ¹H NMR (400 MHz, DMSO-d₆) δ10.60 (s, 1H), 8.04 (dd, J=8.1, 1.7 Hz, 1H), 7.85 (dd, J=7.7, 1.7 Hz,1H), 7.78-7.68 (m, 2H), 7.44 (t, J=7.9 Hz, 1H), 7.23 (dt, J=11.5, 8.9Hz, 2H), 3.88 (s, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ 163.36, 149.49,143.90, 135.07, 133.51, 133.03, 126.15, 124.42, 121.53 (d, J_(CF)=7.8Hz), 115.43 (d, J_(CF)=22.3 Hz), 99.49, 63.30; ESIMS m/z 291 ([M+H]⁺).

2-Chloro-N-(3-fluorophenyl)-N-methyl-5-nitrobenzamide (C169)

Isolated as a yellow solid (1.46 g, 64%): ¹H NMR (400 MHz, CDCl₃) δ 8.02(d, J=8.3 Hz, 2H), 7.42 (d, J=8.5 Hz, 1H), 7.19 (td, J=8.7, 6.6 Hz, 1H),6.96-6.86 (m, 3H), 3.52 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −110.00;ESIMS m/z 309 ([M+H]⁺).

2-Chloro-N-(2-fluorophenyl)-N-methyl-5-nitrobenzamide (C170)

Isolated as a light brown solid (0.61 g, 27%): ¹H NMR (400 MHz, CDCl₃) δ8.13 (dd, J=2.7, 1.3 Hz, 1H), 7.99 (dd, J=8.8, 2.7 Hz, 1H), 7.38 (d,J=8.8 Hz, 1H), 7.25-7.15 (m, 2H), 7.05-6.97 (m, 2H), 3.48 (d, J=0.5 Hz,3H).

2-Chloro-N-(4-cyano-2-methylphenyl)-5-nitrobenzamide (C171)

Isolated as a white solid (1.14 g, 49%): ¹H NMR (400 MHz, DMSO-d₆) δ10.43 (s, 1H), 8.56 (d, J=2.8 Hz, 1H), 8.35 (dd, J=8.8, 2.8 Hz, 1H),7.89 (dd, J=14.0, 8.6 Hz, 2H), 7.79 (d, J=1.9 Hz, 1H), 7.77-7.69 (m,1H), 2.34 (s, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ 163.33, 146.15, 140.02,137.41, 137.00, 134.26, 133.14, 131.25, 130.22, 125.78, 125.48, 124.03,118.76, 107.91, 17.62; ESIMS m/z 316 ([M+H]⁺).

2-Chloro-N-(4-fluoro-2-methylphenyl)-5-nitrobenzamide (C172)

Isolated as a light purple solid (1.45 g, 63%): ¹H NMR (400 MHz,DMSO-d₆) δ 10.20 (s, 1H), 8.50 (d, J=2.8 Hz, 1H), 8.34 (dd, J=8.8, 2.8Hz, 1H), 7.90 (d, J=8.9 Hz, 1H), 7.51 (dd, J=8.8, 5.6 Hz, 1H), 7.16 (dd,J=9.8, 3.0 Hz, 1H), 7.09 (td, J=8.6, 3.0 Hz, 1H), 2.30 (s, 3H); ¹⁹F NMR(376 MHz, CDCl₃) δ −116.56; ESIMS m/z 309 ([M+H]⁺).

N-(4-Fluorophenyl)-6-nitropicolinamide (C173)

Isolated as a light brown solid (0.511 g, 49%): mp 169-170° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 10.62 (s, 1H), 8.68-8.29 (m, 3H), 7.92-7.80 (m,2H), 7.29-7.15 (m, 2H); ESIMS m/z 262 ([M+H]⁺).

N-(4-Fluorophenyl)-4-methyl-3-nitrobenzamide (C174)

Isolated as an off-white solid (0.711 g, 89%): mp 136-138° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 10.52 (s, 1H), 8.57 (d, J=1.8 Hz, 1H), 8.21 (dd,J=8.0, 1.8 Hz, 1H), 7.83-7.74 (m, 2H), 7.69 (d, J=8.1 Hz, 1H), 7.28-7.16(m, 2H), 2.60 (s, 3H); ESIMS m/z 275 ([M+H]⁺).

N-(4-fluorophenyl)-5-nitro-2-(trifluoromethoxy)benzamide (C175)

Isolated as a yellow solid (0.544 g, 75%): mp 175-177° C.; ¹H NMR (400MHz, CDCl₃) δ 8.97 (d, J=2.9 Hz, 1H), 8.43 (dd, J=9.0, 2.9 Hz, 1H), 8.24(s, 1H), 7.63-7.57 (m, 2H), 7.57-7.52 (m, 1H), 7.15-7.07 (m, 2H); ESIMSm/z 345 ([M+H]+).

3-Chloro-N-(4-fluorophenyl)-5-nitrobenzamide (C176)

Isolated as a yellow solid (0.645 g, 84%): mp 209-210° C.; ¹H NMR (400MHz, DMSO-d₆) δ 10.68 (s, 1H), 8.74-8.68 (m, 1H), 8.51 (t, J=2.0 Hz,1H), 8.47 (t, J=1.7 Hz, 1H), 7.84-7.74 (m, 2H), 7.30-7.17 (m, 2H); ESIMSm/z 295 ([M−H]⁻).

2-Chloro-N-(2-chlorophenyl)-5-nitrobenzamide (C177)

Isolated as a yellow solid (1.14 g, 49%): ¹H NMR (400 MHz, CDCl₃) δ 8.69(d, J=2.7 Hz, 1H), 8.53 (dd, J=8.2, 1.5 Hz, 1H), 8.48 (s, 1H), 8.30 (dd,J=8.8, 2.7 Hz, 1H), 7.69 (d, J=8.8 Hz, 1H), 7.45 (dd, J=8.0, 1.5 Hz,1H), 7.42-7.32 (m, 1H), 7.20-7.10 (m, 1H); ¹³C NMR (101 MHz, CDCl₃) δ161.91, 146.79, 137.41, 136.03, 133.91, 131.81, 129.29, 127.97, 126.28,125.87, 125.79, 123.41, 122.01; ESIMS m/z 311 ([M+H]⁺).

2-Chloro-N-(2-isopropylphenyl)-5-nitrobenzamide (C178)

Isolated as a white solid (1.79 g, 75%): ¹H NMR (400 MHz, DMSO-d₆) δ10.21 (s, 1H), 8.45 (d, J=2.7 Hz, 1H), 8.34 (dd, J=8.8, 2.8 Hz, 1H),7.89 (d, J=8.8 Hz, 1H), 7.41 (ddd, J=19.3, 7.6, 1.7 Hz, 2H), 7.27 (dtd,J=18.7, 7.3, 1.6 Hz, 2H), 3.34-3.24 (m, 1H), 1.19 (d, J=6.9 Hz, 6H); ¹³CNMR (101 MHz, DMSO-d₆) δ 163.78, 146.11, 143.95, 138.02, 136.97, 133.74,131.29, 127.35, 127.05, 125.90, 125.71, 125.50, 123.70, 27.19, 23.25;ESIMS m/z 319 ([M+H]⁺).

2-Chloro-N-(2-ethyl-6-methylphenyl)-5-nitrobenzamide (C179)

Isolated as a white solid (1.31 g, 55%): ¹H NMR (400 MHz, DMSO-d₆) δ10.14 (s, 1H), 8.36 (dd, J=8.8, 2.8 Hz, 1H), 8.31 (d, J=2.7 Hz, 1H),7.92 (d, J=8.8 Hz, 1H), 7.24-7.13 (m, 3H), 2.66 (q, J=7.5 Hz, 2H), 2.30(s, 3H), 1.17 (t, J=7.5 Hz, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ 163.25,146.11, 141.22, 137.80, 136.96, 135.68, 133.26, 131.56, 127.89, 127.40,126.30, 125.65, 123.36, 24.41, 18.24, 14.77; ESIMS m/z 319 ([M+H]⁺).

2-Chloro-N-(3-chlorophenyl)-5-nitrobenzamide (C180)

Isolated as an off-white solid (1.46 g, 63%): ¹H NMR (400 MHz, DMSO-d₆)δ 10.90 (s, 1H), 8.51 (d, J=2.7 Hz, 1H), 8.36 (dd, J=8.8, 2.8 Hz, 1H),7.99-7.84 (m, 2H), 7.57 (ddd, J=8.2, 2.0, 1.0 Hz, 1H), 7.42 (t, J=8.1Hz, 1H), 7.22 (ddd, J=8.0, 2.1, 1.0 Hz, 1H); ¹³C NMR (101 MHz, DMSO-d₆)δ 162.99, 146.13, 139.85, 137.29, 137.02, 133.13, 131.36, 130.60,125.88, 123.95, 123.93, 119.24, 118.19; ESIMS m/z 311 ([M+H]⁺).

2-Chloro-N-(2,4-difluorophenyl)-N-methyl-5-nitrobenzamide (C181)

Isolated as a green solid (0.72 g, 36%): ¹H NMR (300 MHz, CDCl₃) δ 8.13(dd, J=2.7, 1.4 Hz, 1H), 8.03 (dd, J=8.8, 2.7 Hz, 1H), 7.40 (dd, J=8.8,0.4 Hz, 1H), 7.24 (td, J=8.9, 5.9 Hz, 1H), 6.84-6.71 (m, 2H), 3.45 (d,J=0.5 Hz, 3H); IR (thin film) 3074, 1654, 1527, 1607 cm⁻¹; ESIMS m/z 327([M+H]⁺).

2-Chloro-N-(4-cyano-2-fluorophenyl)-5-nitrobenzamide (C182)

Isolated as a tan solid (0.642 g, 41%): ¹H NMR (400 MHz, DMSO-d₆) δ11.01 (s, 1H), 8.53 (d, J=2.8 Hz, 1H), 8.41-8.24 (m, 2H), 7.98 (dd,J=10.8, 1.9 Hz, 1H), 7.89 (d, J=8.8 Hz, 1H), 7.77 (ddd, J=8.5, 1.9, 0.9Hz, 1H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −121.17; ESIMS m/z 320 ([M+H]⁺).

Example 29: Preparation of 2-fluoro-N-(4-fluorophenyl)-5-nitrobenzamide(C183)

A solution of 2-fluoro-5-nitrobenzoic acid (1.0 g, 5.40 mmol) in thionylchloride (7.0 mL, 96 mmol) was heated to reflux for 4 hours. Thereaction was then concentrated. Dry toluene (1.0 mL) was added to theresidue twice and concentrated to remove any residual thionyl chloride.The residue was then dissolved in dry dichloromethane (20 mL). Pyridine(0.87 mL, 11 mmol) was added. The solution was cooled in an ice-bath,and 4-fluoroaniline (0.60 g, 5.4 mmol) dissolved in dichloromethane (5.0mL) was added over 20 minutes. The reaction was stirred in the ice-bathfor 45 minutes. The reaction was washed with hydrochloric acid (1 M)(2×20 mL) followed by saturated aqueous sodium bicarbonate (2×20 mL).The organic layer was poured through a phase separator and concentratedto provide the title compound as a white solid (1.2 g, 71%): ¹H NMR (400MHz, CDCl₃) δ 9.07 (dd, J=6.6, 3.0 Hz, 1H), 8.42 (ddd, J=9.0, 4.3, 3.0Hz, 1H), 8.32 (d, J=13.8 Hz, 1H), 7.68-7.59 (m, 2H), 7.40 (dd, J=10.7,9.0 Hz, 1H), 7.16-7.06 (m, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −104.29,−116.18; ESIMS m/z 279 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 29:

2-Fluoro-N-(4-fluorophenyl)-3-nitrobenzamide (C184)

Isolated as a white solid (1.22 g, 81%): ¹H NMR (400 MHz, CDCl₃) δ 8.44(ddd, J=8.3, 6.6, 1.9 Hz, 1H), 8.27 (s, 1H), 8.22 (ddd, J=8.1, 7.3, 1.9Hz, 1H), 7.68-7.57 (m, 2H), 7.49 (td, J=8.0, 1.0 Hz, 1H), 7.16-7.05 (m,2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −116.17, −121.77; EIMS m/z 279 ([M]⁺).

Example 30: Preparation of 2-chloro-5-nitro-N-(pyridin-4-yl)benzamide(C185)

To a solution of 2-chloro-5-nitrobenzoic acid (0.500 g, 2.48 mmol) indichloromethane (8.3 mL) was added oxalyl chloride (0.239 mL, 2.73 mmol)slowly, followed by N,N-dimethylformamide (1 drop). The reaction wasstirred at room temperature for 2 hours. To the solution was addedtriethylamine (0.691 mL, 4.96 mmol) followed by pyridin-4-amine (0.467g, 4.96 mmol) in dichloromethane (1 mL). The reaction was allowed tostir at room temperature for 16 hours. Purification by flash columnchromatography using 0-100% ethyl acetate/hexanes as eluent provided thetitle compound as a tan solid (0.401 g, 58%): ¹H NMR (400 MHz, DMSO-d₆)δ 11.10 (s, 1H), 8.64-8.45 (m, 3H), 8.37 (dd, J=8.9, 2.8 Hz, 1H), 7.92(d, J=8.8 Hz, 1H), 7.73-7.61 (m, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ163.67, 150.56, 146.14, 145.04, 136.95, 131.40, 126.06, 124.00, 113.68;ESIMS m/z 278 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 30:

2-Chloro-5-nitro-N-(pyridin-3-yl)benzamide (C186)

Isolated as a white solid (0.480 g, 70%): ¹H NMR (400 MHz, DMSO-d₆) δ10.95 (s, 1H), 8.85 (dd, J=2.6, 0.7 Hz, 1H), 8.54 (d, J=2.8 Hz, 1H),8.42-8.31 (m, 2H), 8.15 (ddd, J=8.3, 2.6, 1.5 Hz, 1H), 7.92 (d, J=8.8Hz, 1H), 7.44 (ddd, J=8.3, 4.7, 0.8 Hz, 1H); ¹³C NMR (101 MHz, DMSO-d₆)δ 163.19, 146.13, 145.14, 141.29, 137.17, 137.04, 135.17, 131.38,126.78, 125.92, 123.99, 123.76; ESIMS m/z 278 ([M+H]⁺).

2-Chloro-N-(2-chloropyridin-3-yl)-5-nitrobenzamide (C187)

Isolated as a white solid (0.364 g, 47%): ¹H NMR (400 MHz, DMSO-d₆) δ10.67 (s, 1H), 8.53 (d, J=2.8 Hz, 1H), 8.40-8.31 (m, 2H), 8.26 (ddt,J=6.1, 4.5, 2.4 Hz, 1H), 7.91 (d, J=8.9 Hz, 1H), 7.55 (dd, J=7.9, 4.7Hz, 1H); ¹³C NMR (101 MHz, DMSO-d₆) δ 146.77, 146.02, 144.78, 137.16,136.84, 135.87, 131.34, 131.11, 125.95, 124.13, 123.50; ESIMS m/z 312([M+H]⁺).

2-Chloro-N-(6-chloropyridin-3-yl)-5-nitrobenzamide (C188)

Isolated as a white solid (0.639 g, 83%): ¹H NMR (400 MHz, DMSO-d₆) δ11.10 (s, 1H), 8.71 (d, J=2.7 Hz, 1H), 8.56 (d, J=2.7 Hz, 1H), 8.37 (dd,J=8.8, 2.8 Hz, 1H), 8.19 (dd, J=8.7, 2.8 Hz, 1H), 7.92 (d, J=8.8 Hz,1H), 7.57 (d, J=8.7 Hz, 1H); ¹³C NMR (101 MHz, DMSO-d₆) δ 163.20,146.12, 144.54, 140.93, 137.05, 136.85, 134.79, 131.43, 130.44, 126.08,124.39, 124.07; ESIMS m/z 312 ([M+H]⁺).

2-Chloro-N-(6-cyanopyridin-3-yl)-5-nitrobenzamide (C189)

Isolated as a white foam (0.433 g, 58%): ESIMS m/z 303 ([M+H]⁺).

2-Chloro-N-(5-fluoropyridin-2-yl)-5-nitrobenzamide (C190)

Isolated as a light yellow foam (0.094 g, 21%): ¹H NMR (300 MHz,Acetone-d₆) δ 10.29 (s, 1H), 8.56 (d, J=2.7 Hz, 1H), 8.46-8.34 (m, 2H),8.27 (d, J=3.0 Hz, 1H), 7.91-7.81 (m, 1H), 7.82-7.70 (m, 1H); IR (thinfilm) 3112, 1688, 1610, 1576, 1522 cm⁻¹; ESIMS m/z 296 ([M+H]⁺).

5-(2-Chloro-5-nitrobenzamido)-N-methylpicolinamide (C191)

Isolated as a light brown foam (0.330 g, 66%): ¹H NMR (400 MHz, DMSO-d₆)δ 11.16 (s, 1H), 8.90 (d, J=2.4 Hz, 1H), 8.66 (q, J=4.8 Hz, 1H), 8.58(d, J=2.8 Hz, 1H), 8.37 (dd, J=8.9, 2.8 Hz, 1H), 8.30 (dd, J=8.5, 2.4Hz, 1H), 8.07 (d, J=8.5 Hz, 1H), 7.92 (d, J=8.8 Hz, 1H), 2.82 (d, J=4.8Hz, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ 163.92, 163.34, 146.15, 145.63,139.52, 137.32, 137.06, 136.89, 131.43, 127.28, 126.07, 124.09, 122.28,25.90; ESIMS m/z 335 ([M+H]⁺).

2-Chloro-5-nitro-N-(pyridin-4-yl)benzamide (C192)

Isolated as a tan solid (0.401 g, 58%): ¹H NMR (400 MHz, DMSO-d₆) δ11.10 (s, 1H), 8.64-8.45 (m, 3H), 8.37 (dd, J=8.9, 2.8 Hz, 1H), 7.92 (d,J=8.8 Hz, 1H), 7.73-7.61 (m, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ 163.67,150.56, 146.14, 145.04, 136.95, 131.40, 126.06, 124.00, 113.68; ESIMSm/z 278 ([M+H]⁺).

Example 31: Preparation of2-fluoro-N-(4-fluorophenyl)-N-methyl-5-nitrobenzamide (C193)

To a solution of 2-fluoro-5-nitrobenzoic acid (0.500 g, 2.70 mmol) indichloromethane (10 mL) was added oxalyl chloride (0.355 mL, 4.05 mmol)slowly, followed by N,N-dimethylformamide (1 drop). The reaction wasstirred at room temperature for 90 minutes. The reaction mixture wasconcentrated, and the residue was dissolved in dichloromethane (15 mL).To the solution was added pyridine (0.437 mL, 5.40 mmol), and thesolution was cooled to 0° C. To the cool solution was added4-fluoro-N-methylaniline (0.338 g, 2.70 mmol) dissolved indichloromethane (5 mL) over 20 minutes. After 45 minutes the ice bathwas removed, and the reaction was allowed to stir at room temperaturefor 16 hours. The reaction was diluted with dichloromethane and washedwith hydrochloric acid (1 M) (2×20 mL). The organic layer was pouredthrough a phase separator and concentrated to provide the title compoundas a white solid (0.804 g, 92%): ¹H NMR (300 MHz, CDCl₃) δ 8.23 (dd,J=5.5, 2.8 Hz, 1H), 8.13 (ddd, J=9.1, 4.4, 2.8 Hz, 1H), 7.14-7.05 (m,2H), 7.05-6.87 (m, 3H), 3.49 (s, 3H); IR (thin film) 3039, 1647, 1627,1506 cm⁻¹; ESIMS m/z 293 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 31:

2-Fluoro-N-(3-fluorophenyl)-N-methyl-5-nitrobenzamide (C194)

Isolated as a white solid (0.740 g, 94%): ¹H NMR (300 MHz, CDCl₃) δ 8.26(s, 1H), 8.22-8.07 (m, 1H), 7.27-7.13 (m, 1H), 7.03 (t, J=8.6 Hz, 1H),6.99-6.73 (m, 3H), 3.51 (s, 3H); IR (thin film) 3080, 1659, 1629, 1587cm⁻¹.

2-Fluoro-N-(4-fluorophenyl)-N-methyl-3-nitrobenzamide (C195)

Isolated as a yellow solid (0.675 g, 86%): ¹H NMR (300 MHz, CDCl₃) δ7.93 (ddd, J=8.6, 7.1, 1.8 Hz, 1H), 7.56 (ddd, J=7.4, 5.3, 1.8 Hz, 1H),7.19 (td, J=8.0, 1.1 Hz, 1H), 7.08 (ddd, J=8.8, 4.7, 1.2 Hz, 2H),6.99-6.88 (m, 2H), 3.49 (s, 3H); IR (thin film) 3086, 1653, 1614, 1536cm⁻¹; ESIMS m/z 293 ([M+H]⁺).

2-Chloro-4-fluoro-N-(4-fluorophenyl)-5-nitrobenzamide (C196)

Isolated as a yellow solid (0.532 g, 75%): ¹H NMR (300 MHz, CDCl₃) δ8.54 (d, J=7.8 Hz, 1H), 7.85 (s, 1H), 7.66-7.54 (m, 2H), 7.48 (d, J=9.9Hz, 1H), 7.17-7.03 (m, 2H); IR (thin film) 3265, 3072, 1614, 1530 cm⁻¹;ESIMS m/z 313 ([M+H]⁺).

2,4-Difluoro-N-(4-fluorophenyl)-5-nitrobenzamide (C197)

Isolated as a green solid (0.576 g, 79%): ¹H NMR (300 MHz, CDCl₃) δ 9.00(t, J=8.2 Hz, 1H), 8.23 (d, J=13.4 Hz, 1H), 7.67-7.53 (m, 2H), 7.21 (dd,J=10.9, 9.7 Hz, 1H), 7.15-7.06 (m, 2H); IR (thin film) 3080, 1687, 1614,1590 cm⁻¹; ESIMS m/z 297 ([M+H]⁺).

N-(2,4-Difluorophenyl)-2-fluoro-5-nitrobenzamide (C198)

Isolated as a grey solid (3.1 g, 97%): ¹H NMR (400 MHz, CDCl₃) δ 9.08(dd, J=6.6, 3.0 Hz, 1H), 8.56 (d, J=14.5 Hz, 1H), 8.42 (ddt, J=14.1,8.7, 5.0 Hz, 2H), 7.41 (dd, J=10.6, 9.1 Hz, 1H), 6.95 (tdd, J=11.1, 7.0,3.2 Hz, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −104.13, −113.26 (d, J=5.0 Hz),−125.68 (d, J=5.2 Hz); ESIMS m/z 297 ([M+H]⁺).

2-Fluoro-N-methyl-5-nitro-N-phenylbenzamide (C199)

Isolated as a brown oil (1.45 g, 98%): ¹H NMR (400 MHz, CDCl₃) δ 8.21(dd, J=5.6, 2.8 Hz, 1H), 8.15-8.05 (m, 1H), 7.26-7.14 (m, 3H), 7.09 (d,J=7.7 Hz, 2H), 6.98 (t, J=8.6 Hz, 1H), 3.52 (s, 3H); ¹⁹F NMR (376 MHz,CDCl₃) δ −102.19; ESIMS m/z 275 ([M+H]⁺).

2-Fluoro-N-methyl-3-nitro-N-phenylbenzamide (C200)

Isolated as a light brown solid (1.38 g, 93%): ¹H NMR (400 MHz, CDCl₃) δ7.94-7.85 (m, 1H), 7.55 (ddd, J=7.5, 5.4, 1.8 Hz, 1H), 7.26-7.12 (m,4H), 7.08 (d, J=7.6 Hz, 2H), 3.51 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ−118.54; ESIMS m/z 275 ([M+H]⁺).

N-(4-Cyano-2-fluorophenyl)-2-fluoro-5-nitrobenzamide (C201)

Isolated as a light brown solid (1.1 g, 84%): ¹H NMR (400 MHz, DMSO-d₆)δ 10.89 (s, 1H), 8.59 (dd, J=5.8, 2.9 Hz, 1H), 8.49 (ddd, J=9.1, 4.3,3.0 Hz, 1H), 8.24 (t, J=8.1 Hz, 1H), 7.99 (dd, J=10.8, 1.8 Hz, 1H), 7.77(ddd, J=8.4, 1.9, 0.9 Hz, 1H), 7.69 (t, J=9.2 Hz, 1H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −103.66, −120.88; ESIMS m/z 304 ([M+H]⁺).

Example 32: Preparation ofN-(2,4-difluorophenyl)-2-fluoro-N-methyl-5-nitrobenzamide (C202)

To a solution of N-(2,4-difluorophenyl)-2-fluoro-5-nitrobenzamide (C198)(1.00 g, 3.38 mmol) in dry N,N-dimethylformamide (15 mL) cooled in anice bath was added sodium hydride (60% oil immersion, 0.162 g, 4.05mmol). The slurry was stirred for 30 minutes, and iodomethane (0.422 mL,6.75 mmol) was added. The reaction was stirred for 2 hours. Anadditional amount of sodium hydride (0.0400 g) was added. An additionalamount of iodomethane (0.100 mL) was added. The reaction was left tostir for 16 hours. The reaction was quenched by the slow addition ofwater (15 mL) and diluted with ethyl acetate (25 mL). The phases werecut, and the organic layer washed with 1:1 brine/water (3×20 mL). Theorganic layer was dried over magnesium sulfate, filtered, andconcentrated to provide the title compound as a brown oil (1.05 g,quant): ¹H NMR (400 MHz, CDCl₃) δ 8.32-8.24 (m, 1H), 8.15 (ddd, J=9.1,4.3, 2.8 Hz, 1H), 7.23-7.12 (m, 1H), 7.02 (dd, J=9.1, 8.2 Hz, 1H),6.85-6.71 (m, 2H), 3.44 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −102.79 (d,J=5.6 Hz), −107.11 (d, J=8.2 Hz), −115.48 (dd, J=8.3, 5.6 Hz); ESIMS m/z311 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 32:

2-Chloro-N-ethyl-N-(4-fluorophenyl)-5-nitrobenzamide (C203)

Isolated as a tan solid using iodoethane (0.225 g, quant): ¹H NMR (400MHz, CDCl₃) δ 8.02-7.94 (m, 2H), 7.42-7.35 (m, 1H), 7.18-7.11 (m, 2H),6.98-6.86 (m, 2H), 3.97 (q, J=7.2 Hz, 2H), 1.27 (t, J=7.2 Hz, 4H); ¹⁹FNMR (376 MHz, CDCl₃) δ −112.13; ESIMS m/z 323 ([M+H]⁺).

2-Chloro-N-(4-fluorophenyl)-5-nitro-N-(2,2,2-trifluoroethyl)benzamide(C204)

Isolated as a white solid using 2,2,2-trifluoroethylmethanesulfonate(0.147 g, 58%): ¹H NMR (400 MHz, CDCl₃) δ 8.03 (dd, J=8.7, 2.7 Hz, 1H),8.00 (d, J=2.5 Hz, 1H), 7.42 (dd, J=8.8, 0.5 Hz, 1H), 7.25-7.19 (m, 2H),6.99-6.91 (m, 2H), 4.55 (q, J=8.6 Hz, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ−68.62, −110.49; ESIMS m/z 377 ([M+H]⁺).

2-Chloro-N-(4-fluorophenyl)-5-nitro-N-propylbenzamide (C205)

Isolated as a tan solid using iodopropane (0.296 g, quant): ¹H NMR (400MHz, DMSO-d₆) δ 8.32 (d, J=2.8 Hz, 1H), 8.05 (dd, J=8.8, 2.8 Hz, 1H),7.62 (d, J=8.8 Hz, 1H), 7.42-7.34 (m, 2H), 7.15-7.06 (m, 2H), 3.81 (t,J=7.4 Hz, 2H), 1.55 (h, J=7.4 Hz, 2H), 0.93 (t, J=7.4 Hz, 3H); ¹⁹F NMR(376 MHz, DMSO-d₆) δ −113.51; ESIMS m/z 337 ([M+H]⁺).

N-Allyl-2-chloro-N-(4-fluorophenyl)-5-nitrobenzamide (C206)

Isolated as a white solid using 3-bromoprop-1-ene (0.269 g, 91%): ¹H NMR(400 MHz, DMSO-d₆) δ 8.40 (d, J=2.8 Hz, 1H), 8.06 (dd, J=8.9, 2.8 Hz,1H), 7.62 (d, J=8.9 Hz, 1H), 7.43-7.30 (m, 2H), 7.17-7.02 (m, 2H), 5.93(ddt, J=17.2, 10.2, 6.0 Hz, 1H), 5.31-5.11 (m, 2H), 4.47 (d, J=6.0 Hz,2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −113.49; ESIMS m/z 335 ([M+H]⁺).

N-(4-Cyano-2-methylphenyl)-2-fluoro-N-methyl-5-nitrobenzamide (C207)

Isolated as a tan solid (0.595 g, 94%): ¹H NMR (400 MHz, DMSO-d₆) δ8.52-8.17 (m, 2H), 7.94 (d, J=10.1 Hz, 1H), 7.84-7.60 (m, 2H), 7.44 (s,1H), 3.36 (s, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −104.90, −118.40; ESIMSm/z 318 ([M+H]⁺).

2-Chloro-N-(4-cyano-2-fluorophenyl)-N-methyl-5-nitrobenzamide (C208)

Isolated as a white solid (0.826 g, 95%): ESIMS m/z 334 ([M+H]⁺).

Example 33: Preparation of 5-nitro-2-(1H-1,2,4-triazol-1-yl)benzoic acid(C209)

To a solution of methyl 5-nitro-2-(1H-1,2,4-triazol-1-yl)benzoate (C210)(1.24 g, 5.00 mmol) in tetrahydrofuran (25 mL) and water (5.0 mL) wasadded lithium hydroxide (0.359 g, 15.0 mmol). The reaction was stirredat room temperature for 2.5 hours. The reaction was acidified withhydrochloric acid (1 N), and the reaction mixture was extracted withethyl acetate. The combined organic layers were washed with brine, driedover magnesium sulfate, filtered, and concentrated to provide the titlecompound as a faint yellow solid (1.14 g, 93%): ¹H NMR (400 MHz,DMSO-d₆) δ 13.83 (s, 1H), 9.11 (s, 1H), 8.63-8.50 (m, 2H), 8.29 (s, 1H),7.98 (d, J=8.7 Hz, 1H); IR (thin film) 3169, 3097, 1713 cm⁻¹; ESIMS m/z235 ([M+H]⁺).

Example 34: Preparation of methyl5-nitro-2-(1H-1,2,4-triazol-1-yl)benzoate (C210)

To a solution of methyl 2-chloro-5-nitrobenzoate (2.00 g, 9.28 mmol) inN,N-dimethylformamide (18.5 mL) was added 1H-1,2,4-triazole (0.673 g,9.74 mmol). The reaction was stirred at 50° C. for 2 hours, at roomtemperature overnight, and heated at 80° C. for 2 hours. Water wasadded, and the mixture was extracted with diethyl ether. The combinedorganic layers were washed with brine (2×), dried over magnesiumsulfate, filtered, and concentrated to provide the title compound as afaint yellow solid (1.25 g, 51%): ¹H NMR (400 MHz, DMSO-d₆) δ 9.21 (s,1H), 8.62-8.57 (m, 2H), 8.31 (s, 1H), 8.09-8.03 (m, 1H), 3.75 (s, 3H);ESIMS m/z 249 ([M+H]⁺).

Example 35: Preparation of methyl6-[bis(tert-butoxycarbonyl)amino]-3-chloro-pyridine-2-carboxylate (C211)

To a solution of methyl 6-amino-3-chloropicolinate (2.00 g, 10.7 mmol)in tert-butanol (21 mL) and acetone (6.0 mL) was added4-dimethylaminopyridine (0.0200 g, 0.161 mmol) and di-tert-butyldicarbonate (8.21 mL, 35.4 mmol). The reaction was stirred at roomtemperature for 2 days. The reaction was diluted with ethyl acetate,washed with water, dried over magnesium sulfate, filtered, andconcentrated. Purification by flash column chromatography using 0-100%ethyl acetate/hexanes as eluent provided the title compound as a whitesolid (2.45 g, 56%): ¹H NMR (400 MHz, CDCl₃) δ 7.81 (d, J=8.6 Hz, 1H),7.40 (d, J=8.6 Hz, 1H), 3.97 (s, 3H), 1.46 (s, 18H); IR (thin film)2978, 1778, 1742 cm⁻¹; EIMS m/z 387 ([M]⁺).

The following molecules in Table 1 may be prepared according to theprocedures disclosed above.

TABLE P1 Structure and preparation method for prophetic molecules No.Structure Prep* P1

13, 14, 15, 18, 18 P2

13, 14, 15, 18, 18 P3

13, 14, 15, 18 P4

13, 14, 15, 18 P5

13, 14, 15, 18 P6

13, 14, 15, 18 P7

13, 14, 15, 18 P8

13, 14, 15, 18 P9

13 ,14, 15, 18 P10

13, 14, 15, 18 P11

13, 14, 15, 18 P12

13, 14, 15, 18 P13

13, 14, 15, 18 P14

13, 14, 15, 18 P15

13, 14, 15, 18 P16

13, 14, 15, 18 P17

13, 14, 15, 18 P18

13, 14, 15, 18 P19

13, 14, 15, 18 P20

13, 14, 15, 18 P21

Scheme 5 P22

Scheme 5 P23

13, 14, 15, 18 P24

Scheme 5 P25

Scheme 5 P26

Scheme 5 P27

Scheme 5 P28

Scheme 5 P29

Scheme 5 P30

Scheme 5 P31

Scheme 5 P32

13, 14, 15, 18 P33

13, 14, 15, 18 P34

13, 14, 15, 18 P35

13, 14, 15, 18 P36

13, 14, 15, 18 P37

13, 14, 15, 18 P38

13, 14, 15, 18 P39

13, 14, 15, 18 P40

13, 14, 15, 18 P41

13, 14, 15, 18 P42

13, 14, 15, 18 P43

13, 14, 15, 18 P44

13, 14, 15, 18 P45

13, 14, 15, 18 P46

13, 14, 15, 18 P47

13, 14, 15, 18 P48

13, 14, 15, 18 P49

13, 14, 15, 18 P50

13, 14, 15, 18 P51

13, 14, 15, 18 P52

13, 14, 15, 18 P53

13, 14, 15, 18 P54

13, 14, 15, 18 P55

13, 14, 15, 18 P56

13, 14, 15, 18 P57

13, 14, 15, 18 P58

13, 14, 15, 18 P59

13, 14, 15, 18 P60

13, 14, 15, 18 P61

13, 14, 15, 18 P62

13, 14, 15, 18 P63

13, 14, 15, 18 P64

13, 14, 15, 18 P65

13, 14, 15, 18 P66

13, 14, 15, 18 P67

13, 14, 15, 18 P68

13, 14, 15, 18 P69

13, 14, 15, 18 P70

13, 14, 15, 18 P71

13, 14, 15, 18 P72

13, 14, 15, 18 P73

13, 14, 15, 18 P74

13, 14, 15, 18 P75

13, 14, 15, 18 P76

13, 14, 15, 18 P77

13, 14, 15, 18 P78

13, 14, 15, 18 P79

13, 14, 15, 18 P80

13, 14, 15, 18 P81

13, 14, 15, 18 P82

13, 14, 15, 18 P83

13, 14, 15, 18 P84

13, 14, 15, 18 P85

Scheme 6 P86

Scheme 6 P87

Scheme 6 P88

Scheme 6 P89

Scheme 6 P90

Scheme 6 P91

Scheme 6 P92

Scheme 6 P93

Scheme 6 P94

Scheme 6 P95

Scheme 6 P96

Scheme 6 P97

Scheme 6 P98

Scheme 6 P99

Scheme 6 P100

Scheme 6 P101

13, 14, 15, 18 P102

13, 14, 15, 18 P103

Scheme 5 P104

Scheme 5 P105

Scheme 5 P106

Scheme 5 P107

Scheme 5 P108

Scheme 5 P109

Scheme 5 P110

Scheme 5 P111

13, 14, 15, 18 P112

13, 14, 15, 18 P113

13, 14, 15, 18 P114

13, 14, 15, 18 P115

13, 14, 15, 18 P116

13, 14, 15, 18 P117

13, 14, 15, 18 P118

13, 14, 15, 18 P119

13, 14, 15, 18 P120

13, 14, 15, 18 P121

13, 14, 15, 18 P122

13, 14, 15, 18 P123

13, 14, 15, 18 P124

13, 14, 15, 18 P125

13, 14, 15, 18 P126

13, 14, 15, 18 P127

13, 14, 15, 18 P128

13, 14, 15, 18 P129

13, 14, 15, 18 P130

13, 14, 15, 18 P131

13, 14, 15, 18 P132

13, 14, 15, 18 P133

13, 14, 15, 18 P134

13, 14, 15, 18 P135

13, 14, 15, 18 P136

13, 14, 15, 18 P137

13, 14, 15, 18 P138

13, 14, 15, 18 P139

13, 14, 15, 18 P140

13, 14, 15, 18 P141

13, 14, 15, 18 P142

13, 14, 15, 18 P143

13, 14, 15, 18 P144

13, 14, 15, 18 P145

13, 14, 15, 18 P146

13, 14, 15, 18 P147

13, 14, 15, 18 P148

13, 14, 15, 18 P149

13, 14, 15, 18 P150

13, 14, 15, 18 P151

13, 14, 15, 18 P152

13, 14, 15, 18 P153

13, 14, 15, 18 P154

13, 14, 15, 18 P155

13, 14, 15, 18 P156

13, 14, 15, 18 P157

13, 14, 15, 18 P158

13, 14, 15, 18 P159

13, 14, 15, 18 P160

13, 14, 15, 18 P161

Scheme 5 P162

Scheme 5 P163

Scheme 5 P164

Scheme 5 Prep* means prepare according to Example or Scheme

The following compounds were prepared in like manner to the procedureoutlined in Example 2:

trans-2,2-Dichloro-3-(4-methoxyphenyl)cyclopropane-1-carboxylic acid(C212)

Isolated as white crystals (0.090 g, 27%): ¹H NMR (400 MHz, CDCl₃) δ11.33 (s, 1H), 7.22-7.15 (m, 2H), 6.94-6.86 (m, 2H), 3.82 (s, 3H), 3.44(d, J=8.3 Hz, 1H), 2.83 (d, J=8.4 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ172.23, 159.52, 129.77, 124.17, 114.00, 62.40, 55.31, 40.37, 36.97;ESIMS m/z 260 ([M−H]⁻).

trans-3-(4-Bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxylicacid (C213)

Isolated as a brown solid (0.186 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.63(d, J=8.3 Hz, 1H), 7.40-7.32 (m, 1H), 7.04 (ddd, J=8.3, 2.2, 0.7 Hz,1H), 3.42 (d, J=8.3 Hz, 1H), 2.86 (d, J=8.3 Hz, 1H); ¹³C NMR (101 MHz,CDCl₃) δ 171.39, 134.91, 133.89, 133.08, 130.54, 128.16, 122.61, 61.39,39.70, 37.14; ESIMS m/z 342.8 ([M−H]⁻).

trans-3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxylicacid (C214)

Isolated as a tan solid (0.7577 g, 71%): ¹H NMR (400 MHz, CDCl₃) δ 7.53(d, J=J=2.1 Hz, 1H), 7.47 (d, J=8.3 Hz, 1H), 7.17 (dd, J=8.3, 2.1 Hz,1H), 3.44 (d, J=8.3 Hz, 1H), 2.86 (d, J=8.3 Hz, 1H); ¹³C NMR (101 MHz,CDCl₃) δ 171.40, 134.73, 133.87, 132.39, 130.43, 128.70, 122.74, 61.50,39.53, 37.14; ESIMS m/z 342.7 ([M−H]⁻).

trans-3-(3-Bromo-5-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxylicacid (C215)

Isolated as a tan solid (0.9102 mg, 40%): ¹H NMR (400 MHz, Acetone-d₆) δ7.67 (d, J=1.6 Hz, 1H), 7.63 (s, 1H), 7.57 (d, J=1.8 Hz, 1H), 3.53 (d,J=8.5 Hz, 1H), 3.38 (d, J=8.5 Hz, 1H); ¹³C NMR (101 MHz, Acetone-d₆) δ166.92, 138.16, 135.69, 131.59, 131.55, 129.10, 123.23, 62.52, 39.41,37.85; ESIMS m/z 342.7 ([M−H]⁻).

trans-2,2-Dichloro-3-(3-chloro-5-(difluoromethyl)phenyl)cyclopropane-1-carboxylicacid (C216)

Isolated as an off-white solid (2.6 g, 63%): ¹H NMR (300 MHz, CDCl₃)missing COOH signal δ 7.49 (s, 1H), 7.38 (s, 1H), 7.30 (s, 1H), 6.63 (t,J=56.0 Hz, 1H), 3.50 (d, J=8.4 Hz, 1H), 2.91 (d, J=8.0 Hz, 1H); ¹⁹F NMR(282.2 MHz, CDCl₃) δ −112.04; ESIMS m/z 313 ([M−H]⁻).

trans-2,2-Dichloro-3-(4-chloro-3-(difluoromethyl)phenyl)cyclopropane-1-carboxylicacid (C217)

Isolated as an off-white solid (6.2 g, 69%): ¹H NMR (400 MHz, CDCl₃) δ10.5 (br s, 1H), 7.55 (s, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.34 (d, J=8.4Hz, 1H), 6.95 (t, J=54.8 Hz, 1H), 3.50 (d, J=8.4 Hz, 1H), 2.91 (d, J=8.4Hz, 1H); ¹⁹F NMR (376.2 MHz, CDCl₃) δ −115.52; ESIMS m/z 313 ([M−H]⁻).

trans-2,2-Dichloro-3-(3-(difluoromethyl)-5-fluorophenyl)cyclopropane-1-carboxylicacid (C218)

Isolated as an off-white solid (5 g, 38%): ¹H NMR (400 MHz, CDCl₃)missing COOH signal δ 7.23-7.21 (m, 2H), 7.11 (d, J=8.8 Hz, 1H), 6.64(t, J=55.6 Hz, 1H), 3.51 (d, J=8.4 Hz, 1H), 2.91 (d, J=8.0 Hz, 1H); ¹⁹FNMR (376.2 MHz, CDCl₃) δ −110.37; ESIMS m/z 297.19 ([M−H]⁻).

trans-2,2-Dichloro-3-(3-(difluoromethyl)-4-fluorophenyl)cyclopropane-1-carboxylicacid (C219)

Isolated as an off-white solid (6.0 g, 77%): ¹H NMR (400 MHz, CDCl₃)missing COOH signal δ 7.49 (d, J=6.0 Hz, 1H), 7.40 (br s, 1H), 7.17 (t,J=9.2 Hz, 1H), 6.90 (t, J=54.8 Hz, 1H), 3.49 (d, J=8.0 Hz, 1H), 2.89 (d,J=8.4 Hz, 1H); ¹⁹F NMR (376.2 MHz, CDCl₃) δ −114.47, −119.69; ESIMS m/z297 ([M−H]⁻).

trans-2,2-Dichloro-3-(3-chloro-4-(difluoromethyl)phenyl)cyclopropane-1-carboxylicacid (C220)

Isolated as an off-white solid (3.5 g, 42%): ¹H NMR (400 MHz, CDCl₃)missing COOH signal δ 7.68 (d, J=7.6 Hz, 1H), 7.35 (s, 1H), 7.29 (d,J=8.4 Hz, 1H), 6.94 (t, J=54.8 Hz, 1H), 3.48 (d, J=8.4 Hz, 1H), 2.91 (d,J=8.4 Hz, 1H); ¹⁹F NMR (376.2 MHz, CDCl₃) δ −115.46; ESIMS m/z 313([M−H]⁻).

trans-2,2-Dichloro-3-(4-(difluoromethyl)-3-fluorophenyl)cyclopropane-1-carboxylicacid (C221)

Isolated as an off-white solid (4.4 g, 77%): ¹H NMR (400 MHz, CDCl₃) δ7.62 (t, J=7.6 Hz, 1H), 7.18 (d, J=7.6 Hz, 1H), 7.06 (d, J=10.0 Hz, 1H),6.89 (t, J=54.8 Hz, 1H), 3.50 (d, J=8.4 Hz, 1H), 2.90 (d, J=8.4 Hz, 1H);¹⁹F NMR (376.2 MHz, CDCl₃) δ −114.42, −118.63; ESIMS m/z 297.15([M−H]⁻).

trans-2,2-Dichloro-3-(3-(difluoromethyl)phenyl)cyclopropane-1-carboxylicacid (C222)

Isolated as an off-white solid (6.2 g, 53%): ¹H NMR (300 MHz, CDCl₃) δ7.49 (br s, 2H), 7.41 (br s, 2H), 6.66 (t, J=56.0 Hz, 1H), 3.53 (d,J=8.4 Hz, 1H), 2.92 (d, J=8.0 Hz, 1H); ¹⁹F NMR (282.2 MHz, CDCl₃) δ−111.20; ESIMS m/z 279.20 ([M−H]⁻).

trans-2,2-Dichloro-3-(4-(difluoromethyl)phenyl)cyclopropane-1-carboxylicacid (C223)

Isolated as an off-white solid (7 g, 61%): ¹H NMR (300 MHz, CDCl₃) δ7.53 (d, J=8.0 Hz, 2H), 7.37 (d, J=8.0 Hz, 2H), 6.66 (t, J=56.4 Hz, 1H),3.52 (d, J=8.4 Hz, 1H), 2.92 (d, J=8.0 Hz, 1H); ¹⁹F NMR (282.2 MHz,CDCl₃) δ −112.20; ESIMS m/z 279.30 ([M−H]⁻).

trans-3-(4-Bromo-3,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxylicacid (C224)

Isolated as a white solid (2.13 g, 72%): mp 178.3-188.6° C.; ¹H NMR (400MHz, CDCl₃) δ 6.90 (d, J=7.1 Hz, 2H), 3.43 (d, J=8.2 Hz, 1H), 2.86 (d,J=8.2 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −103.87; ESIMS m/z 344.7([M−H]⁻).

trans-3-(4-Bromo-3-fluoro-5-methoxyphenyl)-2,2-dichlorocyclopropane-1-carboxylicacid (C225)

Isolated as an oily solid (0.43 g, 37%): ¹H NMR (400 MHz, CDCl₃) δ6.70-6.64 (m, 1H), 6.61 (d, J=1.6 Hz, 1H), 3.95 (s, 3H), 3.44 (d, J=8.3Hz, 1H), 2.86 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −104.22;ESIMS m/z 356.7 ([M−H]⁻).

trans-3-(3-Bromo-5-fluoro-4-methoxyphenyl)-2,2-dichlorocyclopropane-1-carboxylicacid (C226)

Isolated as a brown oil (0.24 g, 65%): ¹H NMR (400 MHz, CDCl₃) δ 7.24(d, J=7.9 Hz, 1H), 6.87 (d, J=11.3 Hz, 1H), 3.91 (d, J=3.8 Hz, 3H), 3.44(d, J=8.3 Hz, 1H), 2.80 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−135.11; ESIMS m/z 356.7 ([M−H]⁻).

trans-2,2-Dichloro-3-(3,5-difluoro-4-methoxyphenyl)cyclopropane-1-carboxylicacid (C227)

Isolated as a tan solid (0.440 g, 53%): ¹H NMR (400 MHz, CDCl₃) δ 10.72(s, 1H), 6.89-6.77 (m, 2H), 4.02 (t, J=1.2 Hz, 3H), 3.39 (d, J=8.3 Hz,1H), 2.80 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −127.43,−127.43, −127.44; ESIMS m/z 296 ([M−H]⁻).

cis/trans-2,2-Dichloro-3-(3,4,5-trifluorophenyl)cyclopropane-1-carboxylicacid (C228)

Isolated as a white solid (0.411 g, 53%): ¹H NMR (400 MHz, CDCl₃) δ 7.72(s, 1H), 7.06-6.74 (m, 2H), 3.46-3.23 (m, 1H), 3.01-2.74 (m, 1H); ¹⁹FNMR (376 MHz, CDCl₃) δ −132.88, −132.94, −133.81, −133.87, −159.60,−159.65, −159.71, −160.34, −160.39, −160.45; ESIMS m/z 284 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 3:

trans-2-Chloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)thiophene(C229)

Isolated as a dark orange oil (0.455 g, 68%): ¹H NMR (400 MHz, CDCl₃) δ7.25 (d, J=9.5 Hz, 2H), 6.92 (d, J=8.8 Hz, 2H), 6.83 (d, J=3.8 Hz, 1H),6.80 (d, J=3.5 Hz, 1H), 3.83 (s, 3H), 3.10 (s, 2H); ¹³C NMR (101 MHz,CDCl₃) δ 159.40, 136.68, 129.87, 129.36, 126.30, 126.04, 125.59, 113.96,65.28, 55.32, 41.23, 34.95.

trans-2-((2,2-Dichloro-3-methyl-3-(4-(trifluoromethoxy)phenyl)cyclopropyl)methoxy)tetrahydro-2H-pyran(C230)

Isolated as a pale yellow liquid (3.3 g, 77%): ¹H NMR (400 MHz, CDCl₃) δ7.38-7.32 (m, 2H), 7.22-7.16 (d, J=8.4 Hz, 2H), 4.72 (dt, J=17.0, 3.3Hz, 1H), 4.13 (dd, J=11.2, 6.6 Hz, 0.5H), 4.00-3.82 (m, 2H), 3.63 (dd,J=11.3, 7.4 Hz, 0.5H), 3.60-3.52 (m, 1H), 2.20 (dt, J=11.6, 4.5 Hz, 1H),1.94-1.82 (m, 1H), 1.82-1.71 (m, 1H), 1.71-1.55 (m, 4H), 1.52 (d, J=5.9Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) 5-57.85; ¹³C NMR (101 MHz, CDCl₃) δ148.26, 141.31, 130.14, 124.32, 121.77, 120.89, 119.21, 116.65, 99.17,99.08, 67.92, 63.87, 63.77, 62.41, 37.91, 37.83, 36.92, 36.82, 30.74,25.45, 19.93, 19.88, 19.48, 19.44; ESIMS m/z 441.4 (M+CH₃CN); IR (thinfilm) 1257, 1222, 1208, 1163 cm⁻¹.

trans-1-Chloro-3-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-5-(difluoromethyl)benzene(C231)

Isolated as a yellow liquid (11.5 g, 69%): ¹H NMR (300 MHz, CDCl₃): δ7.47 (s, 2H), 7.39 (s, 1H), 7.28 (d, J=8.7 Hz, 2H), 6.93 (d, J=8.7 Hz,2H), 6.64 (t, J=56.1 Hz, 1H), 3.83 (s, 3H), 3.16 (q, J=8.7 Hz, 2H).

trans-1-Chloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-2-(difluoromethyl)benzene (C232)

Isolated as a pale yellow solid (10.7 g, 83%): ¹H NMR (400 MHz, CDCl₃) δ7.65 (s, 1H), 7.46-7.41 (m, 2H), 7.28 (d, J=8.4 Hz, 2H), 7.10-6.83 (m,3H), 3.83 (s, 3H), 3.18-3.13 (m, 2H).

trans-1-(2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)-3-(difluoromethyl)-5-fluorobenzene(C233)

Isolated as an off-white solid (16.5 g, 64%): ¹H NMR (400 MHz, CDCl₃) δ7.29 (d, J=8.8 Hz, 2H), 7.20 (d, J=8.8 Hz, 2H), 6.93 (d, J=8.8 Hz, 2H),6.65 (t, J=56.0 Hz, 2H), 3.83 (s, 3H), 3.16 (s, 2H).

trans-4-(2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)-2-(difluoromethyl)-1-fluorobenzene(C234)

Isolated as an off-white solid (10.0 g, 55%): ESIMS m/z 374 ([M+H]⁺).

trans-2-Chloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-1-(difluoromethyl)benzene(C235)

Isolated as an off-white solid (10.0 g, 34%): ¹H NMR (400 MHz, CDCl₃) δ7.68 (d, J=8.0 Hz, 1H), 7.43 (s, 1H), 7.38 (d, J=8.4 Hz, 1H), 7.28-7.25(m, 2H), 7.09-6.92 (m, 3H), 3.83 (s, 3H), 3.15 (q, J=12.0 Hz, 2H); ESIMSm/z 376 ([M+H]⁺).

trans-2-Fluoro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-1-(difluoromethyl)benzene(C236)

Isolated as a pale yellow liquid (6.9 g, 58%): ¹H NMR (400 MHz, CDCl₃) δ7.31 (t, J=7.6 Hz, 1H), 7.27 (d, J=9.2 Hz, 2H), 7.14 (d, J=10.8 Hz, 1H),7.04-6.76 (m, 4H), 3.83 (s, 3H), 3.16 (t, J=8.8 Hz, 2H); ¹⁹F NMR (376.2MHz, CDCl₃) δ −114.14, −114.32, −119.30.

trans-1-(2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)-3-(difluoromethyl)-benzene(C237)

Isolated as a pale yellow solid (6.3 g, 95%): ¹H NMR (400 MHz, CDCl₃) δ7.50 (br s, 4H), 7.29 (d, J=8.8 Hz, 2H), 6.93 (d, J=8.0 Hz, 2H), 6.67(t, 1H), 3.83 (s, 3H), 3.19 (s, 2H); ¹⁹F NMR (376.2 MHz, CDCl₃) δ−110.87, −111.02.

trans-1-(2,2-Dichloro-3-(4-(difluoromethyl)phenyl)cyclopropyl)-4-methoxybenzene(C238)

Isolated as a white solid (14 g, 69%): ¹H NMR (400 MHz, CDCl₃) δ 7.54(d, J=8.0 Hz, 2H), 7.46 (d, J=8.0 Hz, 2H), 7.28 (t, J=8.4 Hz, 2H), 6.93(d, J=8.0 Hz, 2H), 6.67 (t, J=56.8 Hz, 1H), 3.83 (s, 3H), 3.18 (s, 2H).

The following compounds were prepared in like manner to the procedureoutlined in Example 12:

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoicacid (C239)

Isolated as a grey solid (3.80 g, 96%): ¹H NMR (300 MHz, DMSO-d₆) δ13.48 (s, 1H), 10.90 (s, 1H), 8.15 (d, J=2.6 Hz, 1H), 7.78 (dd, J=8.8,2.7 Hz, 1H), 7.63 (t, J=1.9 Hz, 1H), 7.57-7.50 (m, 3H), 3.62 (d, J=8.5Hz, 1H), 3.49 (d, J=8.5 Hz, 1H); ESIMS m/z 454 ([M+H]⁺).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzoicacid (C240)

Isolated as a grey solid (3.70 g, 98%): ¹H NMR (300 MHz, DMSO-d₆) δ13.47 (s, 1H), 10.95 (s, 1H), 8.16 (d, J=2.7 Hz, 1H), 7.82-7.73 (m, 2H),7.69 (d, J=8.3 Hz, 1H), 7.53 (d, J=8.7 Hz, 1H), 7.43 (dd, J=8.5, 2.1 Hz,1H), 3.60 (d, J=8.5 Hz, 1H), 3.45 (d, J=8.5 Hz, 1H); ESIMS m/z 454([M+H]⁺).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzoicacid (C241)

Isolated as a grey solid (3.60 g, 99%): ¹H NMR (400 MHz, DMSO-d₆) δ13.44 (s, 1H), 10.91 (s, 1H), 8.16 (d, J=2.7 Hz, 1H), 7.80-7.76 (m, 3H),7.54 (d, J=8.7 Hz, 1H), 3.63 (dt, J=8.5, 0.7 Hz, 1H), 3.52 (d, J=8.5 Hz,1H); ESIMS m/z 488 ([M+H]⁺).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzoicacid (C242)

Isolated as a grey solid (3.80 g. 99%): ¹H NMR (400 MHz, DMSO-d₆) δ13.48 (s, 1H), 10.93 (s, 1H), 8.16 (d, J=2.6 Hz, 1H), 7.78 (dd, J=8.8,2.7 Hz, 1H), 7.71 (dd, J=7.2, 2.0 Hz, 1H), 7.53 (d, J=8.7 Hz, 1H),7.50-7.42 (m, 2H), 3.58 (d, J=8.4 Hz, 1H), 3.42 (d, J=8.5 Hz, 1H); ¹⁹FNMR (376 MHz, DMSO-d₆) δ −117.29; ESIMS m/z 438 ([M+H]⁺).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclo-propane-1-carboxamido)benzoicacid (C243)

Isolated as a cream-colored solid (1.565 g, 90%): mp 227-231° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 13.48 (s, 1H), 10.89 (s, 1H), 8.16 (d, J=2.4 Hz,1H), 7.78 (dd, J=8.7, 2.4 Hz, 1H), 7.61 (s, 2H), 7.53 (d, J=8.7 Hz, 1H),3.84 (s, 3H), 3.57 (d, J=8.4 Hz, 1H), 3.45 (d, J=8.5 Hz, 1H); ¹³C NMR(101 MHz, DMSO-d₆) δ 166.27, 162.66, 151.18, 137.58, 131.44, 131.42,131.22, 129.72, 128.18, 125.90, 122.87, 121.16, 62.19, 60.64, 38.51,36.44; HRMS-ESI (m/z) [M+]⁺ calcd for C₁₈H₁₂C₁₅NO₄, 480.9209; found,480.9216.

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzoicacid (C244)

Isolated as a white solid (6.589 g, 93%): 207-210° C.; ¹H NMR (400 MHz,DMSO-d₆) δ 13.50 (s, 1H), 10.95 (s, 1H), 8.18 (d, J=2.5 Hz, 1H), 7.80(dd, J=8.7, 2.5 Hz, 1H), 7.71 (d, J=7.2 Hz, 1H), 7.51 (dd, J=28.2, 8.8Hz, 3H), 3.59 (d, J=8.4 Hz, 1H), 3.43 (d, J=8.5 Hz, 1H); ¹³C NMR (101MHz, DMSO-d₆) δ 166.22, 162.68, 158.01, 155.55, 137.53, 131.37, 131.17,131.00, 130.95, 130.91, 129.74, 129.67, 125.86, 122.82, 121.12, 119.49,119.32, 116.91, 116.70, 62.21, 38.49, 36.58; ¹⁹F NMR (376 MHz, DMSO-d₆)δ −117.26; ESIMS m/z 438 ([M+H]⁺).

trans-2,3-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoicacid (C245)

Isolated as a tan solid (1.685 g, 79%): mp 231-235° C.; ¹H NMR (400 MHz,DMSO-d₆) 13.82 (s, 1H), 11.05 (s, 1H), 8.13 (d, J=2.4 Hz, 1H), 7.97 (d,J=2.4 Hz, 1H), 7.63 (s, 1H), 7.56 (s, 2H), 3.63 (d, J=8.5 Hz, 1H), 3.50(d, J=8.5 Hz, 1H); ¹³C NMR (101 MHz, DMSO-d₆) δ 165.84, 162.96, 138.00,137.09, 134.14, 133.98, 133.01, 127.83, 127.64, 123.41, 122.15, 119.27,61.94, 38.37, 36.78; HRMS-ESI (m/z) [M+]⁺ calcd for C₁₇H₉C₁₆NO₃,484.8714; found, 484.8711.

trans-2,4-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoicacid (C246)

Isolated as a light-yellow solid (0.855 g, 42%): mp 263-266° C.; ¹H NMR(500 MHz, DMSO-d₆) δ 13.67 (s, 1H), 10.37 (s, 1H), 8.37 (s, 1H), 7.85(s, 1H), 7.63 (s, 1H), 7.53 (d, J=1.6 Hz, 2H), 3.82 (d, J=8.6 Hz, 1H),3.63 (d, J=8.5 Hz, 1H); ¹³C NMR (126 MHz, DMSO-d₆) δ 165.41, 163.35,137.17, 133.95, 133.66, 131.17, 129.96, 128.80, 128.24, 127.74, 127.60,126.63, 62.37, 37.24, 37.09; HRMS-ESI (m/z) [M+]⁺ calcd for C₁₇H₉C₁₆NO₃,484.8714; found, 484.8715.

The following compounds were prepared in like manner to the procedureoutlined in Example 13:

trans-2-Chloro-5-(2,2-dibromo-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F162)

Isolated as an off-white solid (0.045 g, 38%).

trans-N-(4-(1H-1,2,3-Triazol-1-yl)phenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F217)

Isolated as an off-white solid (0.062 g, 44%)

trans-tert-Butyl(4-(3-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)carbamate(F262)

Isolated as a yellow foam (0.043 g, 27%)

trans-tert-Butyl(4-(3-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)carbamate(F263)

Isolated as a light yellow foam (0.043 g, 27.2%).

trans-N-(4-(1H-Pyrazol-1-yl)phenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxamido)benzamide(F440)

Isolated as a cream solid (0.310 g, 63%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(oxazol-2-yl)phenyl)benzamide(F446)

Isolated as an off-white solid (0.203 g, 58.4%).

trans-2-Chloro-5-(2,2-dibromo-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(PF7)

Isolated as a pale yellow glass (0.050 g, 29.6%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(trifluoromethyl)-1H-pyrazol-3-yl)benzamide(PF138)

Isolated as an off-white solid (0.092 g, 45.1%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)benzamide(PF139)

Isolated as a colorless glass (0.008 g, 6.37%).

trans-2-Chloro-N-(4-chloropyridin-2-yl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF140)

Isolated as a colorless glass (0.008 g, 6.37%).

trans-2-Chloro-N-(6-chloropyridazin-3-yl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF148)

Isolated as a dark red glass (0.0177 g, 14%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-5-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(PF1)

Isolated as a light yellow oil (0.076 g, 51%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-5-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(PF2)

Isolated as a white foam (0.118 g, 77%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(PF4)

Isolated as a white foam (0.094 g, 67%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(PF5)

Isolated as a light yellow oil (0.097 g, 63%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxamido)-2-ethyl-N-(4-fluorophenyl)benzamide(PF8)

Isolate as a clear film (0.13 g, 54.9%).

trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxamido)-N-(4-fluorophenyl)-2-vinylbenzamide(PF9)

Isolated as a faint yellow film (0.051 g, 20%).

trans-2-Chloro-5-(2,2-dichloro-3-methyl-3-(4-(trifluoromethoxy)phenyl)cyclopropanecarboxamido)-N-(4-fluorophenyl)benzamide(PF32)

Isolated as a white solid (0.017 g, 42%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-chloro-3-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(PF34)

Isolated as a light yellow oil (0.134 g, 95%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-chloro-3-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(PF35)

Isolated as a white foam (0.101 g, 70%).

trans-5-(3-(3-Bromo-5-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)-N-methylbenzamide(PF38)

Isolated as a colorless oil (0.067 g, 64%).

trans-N-(4-Acetamido-2-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF40)

Isolated as a light yellow solid (0.043 g, 31%).

trans-N-(4-Acetamido-2-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF41)

Isolated as a light brown solid (0.078 g, 55%).

trans-N-(4-Acetamido-2-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF42)

Isolated as a white solid (0.085 g, 63%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-methylphenyl)benzamide(PF46)

Isolated as a white solid (0.092 g, 78%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-methylphenyl)benzamide(PF47)

Isolated as a white solid (0.094 g, 75%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-methylphenyl)benzamide(PF48)

Isolated as a white solid (0.077 g, 68%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-methylphenyl)-N-methylbenzamide(PF49)

Isolated as a white solid (0.084 g, 69%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-methylphenyl)-N-methylbenzamide(PF50)

Isolated as a light yellow glass (0.087 g, 73%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(PF65)

Isolated as a white solid (0.052 g, 35.3%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-isopropylphenyl)cyclopropanecarboxamido)-N-(4-fluorophenyl)benzamide(PF66)

Isolated as a white solid (0.051 g, 31.8%).

trans-2-Chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF67)

Isolated as a white foam (0.114 g, 85%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,3,4-trifluorophenyl)benzamide(PF68)

Isolated as a white solid (0.118 g, 87%).

trans-2-Chloro-N-(2-cyanophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF72)

Isolated as a white solid (0.104 g, 80%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(trifluoromethyl)thiazol-2-yl)benzamide(PF134)

Isolated as a white foam (0.096 g, 48%).

trans-2-Chloro-N-(5-chloropyridin-2-yl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF141)

Isolated as a yellow foam (0.068 g, 43%).

trans-N-(4-Acetamido-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF158)

Isolated as a white solid (0.051 g, 37%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-5-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F160)

Isolated as a white foam. (0.064 g, 41%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F161)

Isolated as a white foam (0.031 g, 20%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-chloro-3-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,6-difluorophenyl)benzamide(F163)

Isolated as a white foam (0.052 g, 36%).

trans-5-(3-(3-Bromo-5-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,6-difluorophenyl)benzamide(F164)

Isolated as a white solid (0.018 g, 17%).

trans-2-Chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F190)

Isolated as an orange foam (0.091 g, 80%).

trans-2-Chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F191)

Isolated as a white solid (0.088 g, 73%).

trans-2-Chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F192)

Isolated as an orange glass (0.076 g, 67%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-iodophenyl)benzamide(F193)

Isolated as a white foam (0.121 g, 79%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-iodophenyl)benzamide(F194)

Isolated as a light yellow solid (0.118 g, 77%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoro-4-iodophenyl)benzamide(F203)

Isolated as a white solid (0.133 g, 85%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-fluoro-4-iodophenyl)benzamide(F204)

Isolated as a white solid (0.116 g, 74%).

trans-tert-Butyl-(4-(2-chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)(methyl)carbamate(F218)

Isolated as a white solid (0.104 g, 71%).

trans-tert-Butyl-(4-(2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)(methyl)carbamate(F219)

Isolated as a white solid (0.107 g, 77%).

trans-tert-Butyl-(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-methylbenzamido)-3-methylphenyl)(methyl)carbamate(F220)

Isolated as a white solid (0.127 g, 82%).

trans-tert-Butyl-(4-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-methylbenzamido)-3-methylphenyl)(methyl)carbamate(F221)

Isolated as a white solid (0.101 g, 72%).

trans-2-Chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-methylbenzamide(F243)

Isolated as a white foam (0.084 g, 54%).

trans-2-Chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-methylbenzamide(F244)

Isolated as a white foam (0.088 g, 56%).

5-(trans-3-(4-Bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide(F270)

Isolated as an orange solid. (0.1334 g, 67%).

trans-N-(2-Cyano-4-fluorophenyl)-3-(2,2-dichloro-3-(3,5-dichlorophen pcyclopropane-1-carboxamido)benzamide (F271)

Isolated as a white foam (0.112 g, 78%).

trans-3-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-methylphenyl)benzamide(F272)

Isolated as a white foam (0.117 g, 84%).

trans-3-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F273)

Isolated as a white foam (0.123 g, 87%).

trans-N-(2-Chloro-4-fluorophenyl)-3-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F274)

Isolated as a white solid (0.076 g, 52%).

5-(trans-3-(4-Bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F306)

Isolated as an off-white solid (0.2825 g, 61%).

5-(trans-3-(4-Bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)-N-methylbenzamide(F307)

Isolated as an off-white solid (0.3047 g, 62%).

trans-5-(3-(3,5-bis(Trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2-cyano-4-fluorophenyl)benzamide(F308)

Isolated as a white solid (0.080 g, 58%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F309)

Isolated as a white solid (0.059 g, 39%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F310)

Isolated as a white solid (0.062 g, 41%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F311)

Isolated as a white solid (0.054 g, 37%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F316)

Isolated as a white solid (0.071 g, 46%).

5-(trans-3-(4-Bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2-cyano-4-fluorophenyl)benzamide(F320)

Isolated as a white foam (0.1212 g, 4261%).

tert-Butyl(4-(5-(trans-3-(4-bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-3-methylphenyl)(methyl)carbamate(F321)

Isolated as a white solid (0.2009 g, 61%).

tert-Butyl(4-(5-(trans-3-(4-bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-3-methylphenyl)carbamate(F322)

Isolated as a white foam (0.0812 g, 25%).

5-(trans-3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide(F330)

Isolated as a pale yellow foam (0.1740 g, 64%).

5-(trans-3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F331)

Isolated as a pale yellow foam (0.1959 g, 70%).

5-(trans-3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2-cyano-4-fluorophenyl)benzamide(F332)

Isolated as a pale yellow foam (0.1893 g, 67%).

5-(trans-3-(3-Bromo-5-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2-cyano-4-fluorophenyl)benzamide(F333)

Isolated as a pale yellow foam (0.226 g, 77%).

tert-Butyl(4-(5-(trans-3-(3-bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-3-methylphenyl)carbamate(F334)

Isolated as a pale yellow foam (0.1789 g, 54%).

tert-Butyl(4-(5-(trans-3-(3-bromo-5-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-3-methylphenyl)carbamate(F335)

Isolated as a pale yellow foam (0.2256 g, 68%).

trans-2-Chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide(F340)

Isolated as a white solid (0.106 g, 69%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-5-cyanophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F342)

Isolated as a light yellow foam (0.061 g, 40%).

trans-2-Chloro-N-(2-cyano-4-fluorophenyl)-5-(2,2-dichloro-3-(3-chloro-5-cyanophenyl)cyclopropane-1-carboxamido)benzamide(F343)

Isolated as a white solid (0.082 g, 53%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-(prop-2-yn-1-yl)benzamide(F413)

Isolated as a white foam (0.117 g, 75%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)-N-(prop-2-yn-1-yl)benzamide(F414)

Isolated as a light yellow foam (0.131 g, 79%).

trans-2-Chloro-5-(2,2-dichloro-3-(4-nitrophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F422)

Isolated as a white solid (0.207 g, 80%/).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)carbamate(F500)

Isolated as a white solid (0.174 g, 67%/).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)carbamate(F501)

Isolated as a white solid (0.171 g, 64%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)carbamate(F503)

Isolated as a white solid (0.161 g, 75%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(5-(3-(4-bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,6-difluorophenyl)carbamate(F512)

Isolated as a white foam (0.2060 g, 55%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(5-(3-(3-bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,6-difluorophenyl)carbamate(F513)

Isolated as a pale yellow solid (0.2054 g, 54%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(5-(3-(3-bromo-5-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,6-difluorophenyl)carbamate(F514)

Isolated as a pale yellow foam (0.3134 g, 83%).

trans-tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(2-chloro-5-(2,2-dichloro-3-(3-chloro-5-cyanophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)carbamate(F515)

Isolated as a white solid (0.133 g, 63%).

trans-tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(2-chloro-5-(2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)carbamate(F516)

Isolated as a white solid (0.187 g, 90%).

5-(trans-3-(3-Bromo-5-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide(PF37)

Isolated as a pale yellow foam (0.2287 g, 84%).

5-(trans-3-(3-Bromo-5-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(PF39)

Isolated as a pale yellow foam (0.2352 g, 84%).

trans-tert-Butyl(4-(2-chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)carbamate(F606)

Isolated as a white solid (0.068 g, 47%).

trans-tert-Butyl(4-(2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)carbamate(F607)

Isolated as a white solid (0.069 g, 51%).

5-(trans-3-(4-bromo-3,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide(F538)

Isolated as a yellow foam (0.1445 g, 40%).

5-(trans-3-(4-Bromo-3-fluoro-5-methoxyphenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide(F539)

Isolated as a yellow foam (0.0322 g, 23%).

5-(trans-3-(3-Bromo-5-fluoro-4-methoxyphenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide(F540)

Isolated as a yellow foam (0.0243 g, 17%).

5-(trans-3-(4-Bromo-3,5-difluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F541)

Isolated as a yellow foam (0.1307 g, 88%).

5-(trans-3-(4-Bromo-3-fluoro-5-methoxyphenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F542)

Isolated as a yellow foam 0.01 g, 49%).

5-(trans-3-(3-Bromo-5-fluoro-4-methoxyphenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F543)

Isolated as a yellow foam (0.0273 g, 19%).

5-((1R,3R)-3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F572)

Isolated as a yellow foam (0.0886 g, 68%).

5-((1S,3S)-3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F573)

Isolated as a yellow foam (0.0833 g, 64%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(5-((1R,3R)-3-(3-bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,6-difluorophenyl)carbamate(F616)

Isolated as a white foam (0.1054 g, 60%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(5-(5-((1R,3R)-3-(3-bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamido)-2,4-difluorophenyl)carbamate(F617)

Isolated as a yellow foam (0.0506 g, 29%).

5-(trans)-2-Bromo-2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide(PF33)

Isolated as a white solid (0.069 mg, 48%).

5-(trans)-2-Bromo-3-(3,5-dichlorophenyl)-2-fluorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide(PF51)

Isolated as a pale yellow solid (0.095 g, 53%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,4,5-trichlorophenyl)benzamide(PF119)

Isolated as a white solid (0.031 g, 22%).

2-Chloro-5-(trans)-2-chloro-3-(3,5-dichlorophenyl)-2-fluorocyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(PF153)

Isolated as a white foam (0.152 g, 73%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3-chloro-5-cyanophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(PF155)

Isolated as a white solid (0.104 g, 55%).

The following compounds were prepared in like manner to the procedureoutlined in Example 14:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)-N-methylcyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F183)

Isolated as a brown waxy solid (0.033 g, 23%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-3-(trifluoromethyl)phenyl)benzamide(PF70)

Isolated as a light brown foam (0.111 g, 29.2%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(trifluoromethyl)phenyl)benzamide(PF71)

Isolated as a light brown foam (0.147 g, 26.8%)

trans-2-Chloro-N-(4-chloro-3-methylphenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF113)

Isolated as a white foam (0.091 g, 70.1%).

2-Chloro-N-(4-chloro-3-methoxyphenyl)-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF114)

Isolated as a white foam (0.095 g, 71.2%).

N-(4-Bromo-3-fluorophenyl)-2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF115)

Isolated as a white foam (0.059 g, 41.9%).

2-Chloro-N-(4-chloro-2-fluorophenyl)-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF116)

Isolated as a white foam (0.091 g, 69.6%).

2-Chloro-5-(4-chloro-2-fluorophenyl)-5-trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,4-dichlorophenyl-)benzamide(PF17)

Isolated as a white foam (0.030 g, 22%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,5-difluorophenyl)benzamide(PF118)

Isolated as a white foam (0.040 g, 31.5%).

2-Chloro-N-(3-chloro-4-cyanophenyl)-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF120)

Isolated as a white foam (0.020 g, 15%).

2-Chloro-N-(3-chloro-4-fluorophenyl)-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF122)

Isolated as a gold foam (0.093 g, 71.2%).

2-Chloro-N-(4-chloro-3-fluorophenyl)-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF123)

Isolated as a white foam (0.084 g, 64.3%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-ethynylphenyl)benzamide(PF124)

Isolated as a yellow foam (0.084 g, 56.2%).

2-Chloro-N-(3-chloro-4-methylphenyl)-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF125)

Isolated as a white foam (0.107 g, 68.6%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1H-indol-6-ylbenzamide(PF126)

Isolated as a white solid (0.055 g, 35.9%).

2-Chloro-N-(3,4-dichloro-2-fluorophenyl)-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF127)

Isolated as a white foam (0.016 g, 9.62%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F165)

Isolated as a white foam (0.0242 g, 52.1%).

2-Chloro-5-((1S,3S)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F166)

Isolated as a white foam (0.221 g, 48.5%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F169)

Isolated as a white foam (0.095 g, 52.9%).

2-Chloro-5-((1S,3S)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F170)

Isolated as a white foam (0.103 g, 57.3%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F185)

Isolated as a white foam (0.200 g, 52.1%).

3-(trans)-2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F186)

Isolated as a white foam (0.184 g, 68%).

2-Chloro-5-((1S,3S)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F208)

Isolated as a white foam (0.090 g, 34.9%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido-N-(4-fluorophenyl)benzamide(F209)

Isolated as a white foam (0.086 g, 33.4%).

2-Chloro-5-((1S,3S)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F210)

Isolated as a white foam (0.096 g, 36.1%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F211)

Isolated as a white foam (0.076 g, 28.6%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methylisoindolin-5-yl)benzamide(F498)

Isolated as a tan foam (0.073 g, 53.9%).

2-Chloro-5-(2,2-dichloro-3-cis-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F629)

Isolated as an off-white solid (0.027 g, 29%).

The following compounds were prepared in like manner to the procedureoutlined in Example 15:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-3-methoxyphenyl)benzamide(PF52)

Isolated as a white foam (0.080 g, 78%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-3,5-dimethylphenyl)benzamide(PF53)

Isolated as a white solid (0.056 g, 55%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2,3-dimethylphenyl)benzamide(PF54)

Isolated as a white solid (0.064 g, 63%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluoro-3-methylphenyl)benzamide(PF55)

Isolated as a white solid (0.038 g, 37%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-methoxyphenyl)benzamide(PF58)

Isolated as a white solid (0.048 g, 47%).

trans-methyl(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)phenyl)carbamate(PF110)

Isolated as a white foam (0.096 g, 72%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(thiophen-3-yl)benzamide(PF152)

Isolated as an off-white glass (0.096 g, 81%).

trans-tert-Butyl-(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)carbamate(F197)

Isolated as a white solid (0.056 g, 55%).

trans-tert-Butyl-(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)(methyl)carbamate(F198)

Isolated as a white solid (0.169 g, 44%).

trans-N-(Benzo[b]thiophen-5-yl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F452)

Isolated as an off-white foam (0.125 g, 81%).

trans-N-(Benzo[d]thiazol-5-yl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F482)

Isolated as a white powder (0.092 g, 59%).

trans-tert-Butyl(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-fluorophenyl)(methyl)carbamate(F600)

Isolated as a white solid (0.066 g, 22%).

trans-tert-Butyl-N-((tert-butoxy)carbonyl)-N-(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2-fluorophenyl)carbamate(F601)

Isolated as a white foam (0.093 g, 55%).

trans-tert-Butyl-N-((tert-butoxy)carbonyl)-N-(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-fluorophenyl)carbamate(F602)

Isolated as a white foam (0.029 g, 17%).

trans-tert-Butyl(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2-fluorophenyl)(methyl)carbamate(F603)

Isolated as a white foam (0.090 g, 60.3%)

trans-tert-Butyl(3-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)phenyl)carbamate(F604)

Isolated as a colorless glass (0.091 g, 68%).

trans-tert-Butyl(3-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)phenyl)(methyl)carbamate(F605)

Isolated as a colorless glass (0.074 g, 54%).

trans-tert-Butyl(5-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2-methoxyphenyl)carbamate(F608)

Isolated as a pink solid (0.121 g, 87%).

trans-tert-Butyl(5-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2-methoxyphenyl)(methyl)carbamate(F609)

Isolated as an orange solid (0.122 g, 86%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(methylthio)-1H-1,2,4-triazol-3-yl)benzamide(F184)

Isolated as an off-white solid (0.082 g, 59%)

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(thiazol-2-yl)phenyl)benzamide(F461)

Isolated as an off-white foam (0.085 g, 59.4%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(p-tolyl)thiazol-2-yl)benzamide(PF136)

Isolated as an off-white solid (0.087 g, 56.7%).

trans-tert-Butyl(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2-methylphenyl)(methyl)carbamate(F618)

Isolated as an off-white foam (0.041 g, 43%).

trans-tert-Butyl(5-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2-methylphenyl)(methyl)carbamate(F619)

Isolated as an off-white foam (0.064 g, 75%).

trans-tert-Butyl(5-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2-methylphenyl)carbamate(F620)

Isolated as an off-white foam (0.104 g, 52%).

5-(trans)-2-Bromo-2-chloro-3-(3,5-dichlorophenyl)cyclopropanecarboxamido)-2-chloro-N-(4-fluorophenyl)-N-methylbenzamide(F167)

Isolated as a white foam (0.128 g, 71.4%).

5-(trans)-2-Bromo-2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-chloro-N-(2,6-difluorophenyl)benzamide(F168)

Isolated as a white foam (0.096 g, 54.3%).

N-(5-Bromo-1H-indol-6-yl)-2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F172)

Isolated as a white foam (0.081 g, 27.8%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-V-(4-fluoro-1H-indol-6-yl)benzamide(F173)

Isolated as a gold oil (0.114 g, 41.9%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1H-pyrrolo[2,3-b]pyridin-6-yl)benzamide(F178)

Isolated as a white solid (0.121 g, 49.2%).

5-(trans)-2-Bromo-2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F187)

Isolated as a white foam (0.171 g, 63.2%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3-chloro-5-cyanophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F188)

Isolated as a white solid (0.105 g, 53.8%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3-chloro-5-cyanophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F189)

Isolated as a gold foam (0.125 g, 64.6%).

2-Chloro-5-((2S)-2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F212)

Isolated as a white solid (0.073 g, 27.7%).

2-Chloro-5-((2R)-2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F213)

Isolated as a white solid (0.078 g, 29.5%).

2-Chloro-5-((2S)-2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F214)

Isolated as a white solid (0.097 g, 33.9%).

2-Chloro-5-((2R)-2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F215)

Isolated as a white solid (0.109 g, 38.1%).

N-(Benzo[d]thiazol-6-yl)-2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F434)

Isolated as a white foam (0.055 g, 41.7%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1H-indol-5-yl)benzamide(F435)

Isolated as a tan foam (0.030 g, 11.7%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(quinolin-7-yl)benzamide(F436)

Isolated as a tan foam (0.121 g, 46.4%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1H-pyrrolo[3,2-b]pyridin-6-yl)benzamide(F437)

Isolated as a tan foam (0.137 g, 53.5%).

2-Chloro-N-(2-chloro-1H-benzo[d]imidazol-6-yl)-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F438)

Isolated as a pale yellow solid (0.101 g, 37.2%).

N-(Benzo[d]thiazol-2-yl)-2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F441)

Isolated as a white solid (0.038 g, 19.22%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-fluorobenzo[d]thiazol-2-yl)benzamide(F442)

Isolated as a white solid (0.109 g, 53.5%).

2-Chloro-N-(4-chlorobenzo[d]thiazol-2-yl)-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F443)

Isolated as a white solid (0.073 g, 34.9%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5,6-dichlorobenzo[d]thiazol-2-yl)benzamide(F444)

Isolated as a white solid (0.097 g, 43.9%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(6-fluorobenzo[d]thiazol-2-yl)benzamide(F445)

Isolated as a white solid (0.122 g, 59.9%).

N-(Benzo[d]oxazol-2-yl)-2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F447)

Isolated as a white solid (0.032 g, 16.6%).

2-Chloro-N-(5-chlorobenzo[d]oxazol-2-yl)-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F448)

Isolated as a white solid (0.062 g, 30.4%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-1-methyl-1H-indazol-3-yl)benzamide(F449)

Isolated as a white foam (0.020 g, 9.9%).

N-(Benzo[d]oxazol-6-yl)-2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F450)

Isolated as a tan foam (0.028 g, 14.6%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(6-fluoro-1H-benzo[d]imidazol-2-yl)benzamide(F451)

Isolated as a tan foam (0.073 g, 36.9%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-fluorobenzo[d]oxazol-6-yl)benzamide(F453)

Isolated as a clear colorless oil (0.020 g, 10.1%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-1H-indol-5-yl)benzamide(F454)

Isolated as a yellow foam (0.142 g, 72.3%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methylbenzo[d]thiazol-5-yl)benzamide(F455)

Isolated as a white solid (0.063 g, 31.1%).

N-(1H-Benzo[d]imidazol-5-yl)-2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F456)

Isolated as a white solid (0.037 g, 19.3%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1-methyl-1H-indol-5-yl)benzamide(F457)

Isolated as a tan solid (0.133 g, 67.7%).

2-Chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(imidazo[1,2-a]pyridin-6-yl)benzamide(F475)

Isolated as a pale blue solid (0.057 g, 43.2%).

trans-N-(3-(3-Amino-6-cyano-1H-indazole-1-carbonyl)-4-chlorophenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide(F493)

Isolated as a tan solid (0.066 g, 47.9%).

The following compounds were prepared in like manner to the procedureoutlined in Example 17:

trans-N-(4-(1H-Imidazol-1-yl)phenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF56)

Isolated as an off-white foam/glass (0.066 g, 49.8%)

trans-N-(4-(1H-1,2,4-Triazol-1-yl)phenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF57)

Isolated as a pink foam (0.080 g, 60.2%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-diethyl-4-(perfluorobutan-2-yl)phenyl)benzamide(PF59)

Isolated as an off-white solid (0.030 g, 16.8%)

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-dimethyl-4-(perfluoropropan-2-yl)phenyl)benzamide

Isolated as an off-white solid (0.050 g, 29.3%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,6-diethyl-4-(perfluoropropan-2-yl)phenyl)benzamide(PF61)

Isolated as a light brown foam/glass (0.054 g, 32.2%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2,2,2-trifluoroethoxy)phenyl)benzamide(PF62)

Isolated as a white solid (0.074 g, 50.2%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-nitrophenyl)benzamide(PF73)

Isolated as an off-white foam (0.035 g, 27.4%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoro-4-nitrophenyl)benzamide(PF74)

Isolated as a pale yellow glass (0.016 g, 11.5%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-nitrophenyl)benzamide(PF75)

Isolated as a yellow foam (0.028 g, 20.24%).

trans-N-(4-(4H-1,2,4-Triazol-4-yl)phenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF102)

Isolated as an off-white solid (0.050 g, 35.7%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1H-tetrazol-5-yl)benzamide(PF130)

Isolated as a white solid (0.027 g, 8.81%).

The following compounds were prepared in like manner to the procedureoutlined in Example 18:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-((2,2,2-trifluoroethyl)thio)phenyl)benzamide(PF10)

Isolated as a tan solid (0.294 g, 69%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-((trifluoromethyl)thio)phenyl)benzamide(PF11)

Isolated as a tan solid (0.273 g, 66%/).

trans-tert-Butyl-(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)phenyl)(methyl)carbamate(PF12)

Isolated as a white solid (0.278 g, 64%/).

trans-tert-Butyl-(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)phenyl)carbamate(PF13)

Isolated as a white foam (0.273 g, 45%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(N-methylacetamido)phenyl)benzamide(PF14)

Isolated as a white solid (0.098 g, 74%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-ethynylphenyl)benzamide(PF15)

Isolated as a tan solid (0.095 g, 78%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-vinylphenyl)benzamide(PF16)

Isolated as a tan solid (0.094 g, 77%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2,6-dimethylphenyl)benzamide(PF43)

Isolated as a light brown solid (0.034 g, 28%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-3-methylphenyl)benzamide(PF44)

Isolated as a light brown solid (0.074 g, 62%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-thiocyanatophenyl)benzamide(PF45)

Isolated as an orange foam (0.032 g, 26%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-dichlorophenyl)benzamide(PF76)

Isolated as a light brown foam (0.025 g, 20%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(dimethylamino)phenyl)benzamide(F171)

Isolated as a yellow solid (0.045 g, 37%).

The following compounds were prepared in like manner to the procedureoutlined in Example 23:

5-Amino-N-(4-fluorophenyl)-2-vinylbenzamide (C247)

Isolated as a yellow solid (0.053 g, 89%): ¹H NMR (400 MHz, CDCl₃) δ7.62 (s, 1H), 7.53 (dd, J=8.9, 4.7 Hz, 2H), 7.37 (d, J=8.4 Hz, 1H), 7.02(t, J=8.6 Hz, 2H), 6.92 (dd, J=17.4, 10.9 Hz, 1H), 6.77 (d, J=2.1 Hz,1H), 6.70 (dd, J=8.3, 2.2 Hz, 1H), 5.56 (d, J=17.4 Hz, 1H), 5.18 (d,J=11.1 Hz, 1H), 3.86 (s, 2H); IR (thin film) 3279, 1651 cm⁻¹; ESIMS m/z257 ([M+H]⁺).

5-Amino-2-chloro-N-(2-cyano-4-fluorophenyl)benzamide (C248)

Isolated as a white solid (0.272 g, 100%): ¹H NMR (400 MHz, DMSO-d₆) δ10.66 (s, 1H), 7.89 (dd, J=8.5, 3.0 Hz, 1H), 7.72-7.50 (m, 2H), 7.15 (d,J=8.6 Hz, 1H), 6.76 (d, J=2.8 Hz, 1H), 6.67 (dd, J=8.6, 2.8 Hz, 1H),5.53 (s, 2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −114.72; ESIMS m/z 290([M+H]⁺).

5-Amino-2-chloro-N-(2,3,4-trifluorophenyl)benzamide (C249)

Isolated as a white solid (0.257 g, 94%): ¹H NMR (400 MHz, DMSO-d₆) δ10.40 (s, 1H), 7.51-7.43 (m, 1H), 7.34 (tdd, J=9.9, 8.1, 2.2 Hz, 1H),7.14 (d, J=8.6 Hz, 1H), 6.74 (d, J=2.7 Hz, 1H), 6.66 (dd, J=8.6, 2.8 Hz,1H), 5.50 (s, 2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −138.77 (dd, J=22.1, 4.5Hz), −140.67 (dd, J=21.1, 4.5 Hz), −160.53 (t, J=21.6 Hz); ESIMS m/z 301([M+H]⁺).

5-Amino-2-chloro-N-(2-cyanophenyl)benzamide (C250)

Isolated as a white solid (0.224 g, 83%): ¹H NMR (400 MHz, DMSO-d₆) δ10.66 (s, 1H), 7.86 (dd, J=7.8, 1.5 Hz, 1H), 7.73 (td, J=7.8, 1.6 Hz,1H), 7.55 (d, J=8.2 Hz, 1H), 7.42 (td, J=7.6, 1.2 Hz, 1H), 7.15 (d,J=8.6 Hz, 1H), 6.77 (d, J=2.7 Hz, 1H), 6.67 (dd, J=8.6, 2.8 Hz, 1H),5.53 (s, 2H); IR (thin film) 3361, 2227, 1672, 1520 cm⁻¹; ESIMS m/z 272([M+H]⁺).

5-Amino-2-chloro-N-(4-(trifluoromethyl)thiazol-2-yl)benzamide (C251)

Isolated as a brown solid (0.135 g, 84%): ¹H NMR (300 MHz, DMSO-d₆) δ13.01 (s, 1H), 8.05 (dd, J=2.7, 1.6 Hz, 1H), 7.16 (d, J=8.6 Hz, 1H),6.74 (d, J=2.7 Hz, 1H), 6.69 (dd, J=8.6, 2.8 Hz, 1H), 5.54 (s, 2H); IR(thin film) 1663, 1544, 1236 cm⁻¹; ESIMS m/z 322 ([M+H]⁺).

5-Amino-2-chloro-N-(5-chloropyridin-2-yl)benzamide (C252)

Isolated as a yellow solid (0.083 g, 60%): ¹H NMR (300 MHz, DMSO-d₆) δ11.13 (s, 1H), 8.34 (dd, J=5.4, 0.6 Hz, 1H), 8.25 (d, J=1.9 Hz, 1H),7.31 (dd, J=5.4, 1.9 Hz, 1H), 7.11 (d, J=8.6 Hz, 1H), 6.69 (d, J=2.7 Hz,1H), 6.64 (dd, J=8.6, 2.7 Hz, 1H), 5.47 (s, 2H); IR (thin film) 3359,3223, 1675, 1565 cm⁻¹; ESIMS m/z 282 ([M+H]⁺).

5-Amino-2-chloro-N-(4-iodophenyl)benzamide (C253)

Isolated as a red solid (0.302 g, 99%): ¹H NMR (300 MHz, DMSO-d₆) δ10.48 (s, 1H), 7.73-7.63 (m, 2H), 7.61-7.51 (m, 2H), 7.13 (d, J=8.5 Hz,1H), 6.71-6.61 (m, 2H), 5.48 (s, 2H); IR (thin film) 3357, 1662, 1597,1524 cm⁻¹; ESIMS m/z 373 ([M+H]⁺).

5-Amino-2-chloro-N-(3-iodophenyl)benzamide (C254)

Isolated as a dark brown solid (0.320 g, 100%): ¹H NMR (300 MHz,DMSO-d₆) δ 10.48 (s, 1H), 8.22 (t, J=1.9 Hz, 1H), 7.71-7.58 (m, 1H),7.46 (ddd, J=7.8, 1.7, 0.9 Hz, 1H), 7.18-7.09 (m, 2H), 6.73-6.60 (m,2H), 5.49 (s, 2H); IR (thin film) 3394, 3158, 1656, 1582, 1530 cm⁻¹;ESIMS m/z 373 ([M+H]⁺).

5-Amino-2-chloro-N-(2-fluoro-4-iodophenyl)benzamide (C255)

Isolated as a cream-colored solid (0.238 g, 73%): ¹H NMR (400 MHz,DMSO-d₆) δ 10.24 (s, 1H), 7.76-7.68 (m, 1H), 7.56 (d, J=6.7 Hz, 2H),7.12 (d, J=8.6 Hz, 1H), 6.71 (d, J=2.7 Hz, 1H), 6.64 (dd, J=8.6, 2.7 Hz,1H), 5.47 (s, 2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −119.45; ESIMS m/z 391([M+H]⁺).

5-Amino-2-chloro-N-(3-fluoro-4-iodophenyl)benzamide (C256)

Isolated as a light brown foam (0.267 g, 93%): ¹H NMR (400 MHz, DMSO-d₆)δ 10.68 (s, 1H), 7.82-7.71 (m, 2H), 7.31 (dd, J=8.6, 2.3 Hz, 1H), 7.14(d, J=8.5 Hz, 1H), 6.70-6.63 (m, 2H), 5.50 (s, 2H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −93.94; ESIMS m/z 391 ([M+H]⁺).

5-Amino-2-chloro-N-(2-cyano-4-fluorophenyl)-N-methylbenzamide (C257)

Isolated as a yellow foam (0.200 g, 99%): ¹H NMR (400 MHz, DMSO-d₆) δrotamers 8.01 (dd, J=8.4, 2.9 Hz, 1H), 7.79-7.63 (m, 2H), 7.28 (d, J=8.7Hz, 0.4H), 7.17 (d, J=8.5 Hz, 0.6H), 6.68-6.61 (m, 1H), 6.41 (dd, J=8.7,2.7 Hz, 1H), 5.58 (s, 0.8H), 5.37 (s, 1.2H), 3.16 (d, J=1.5 Hz, 3H); ¹⁹FNMR (376 MHz, DMSO-d₆) δ rotamers −112.21, −112.23; ESIMS m/z 304([M+H]⁺).

3-Amino-N-(2-cyano-4-fluorophenyl)benzamide (C258)

Isolated as a white solid (0.252 g, 91%): ¹H NMR (400 MHz, DMSO-d₆) δ10.40 (s, 1H), 7.88 (dd, J=8.4, 3.0 Hz, 1H), 7.73-7.50 (m, 2H),7.25-7.04 (m, 3H), 6.79 (ddd, J=7.9, 2.4, 1.1 Hz, 1H), 5.37 (s, 2H); ¹⁹FNMR (376 MHz, DMSO-d₆) δ −115.13; ESIMS m/z 256 ([M+H]⁺).

3-Amino-N-(4-fluoro-2-methylphenyl)benzamide (C259)

Isolated as a purple solid (0.297 g, 95%): ¹H NMR (400 MHz, DMSO-d₆) δ9.66 (s, 1H), 7.31 (dd, J=8.7, 5.6 Hz, 1H), 7.17-7.07 (m, 4H), 7.03 (td,J=8.6, 3.1 Hz, 1H), 6.74 (dd, J=7.6, 2.1 Hz, 1H), 5.30 (s, 2H), 2.21 (s,3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −117.38; ESIMS m/z 245 ([M+H]⁺).

3-Amino-N-(4-fluorophenyl)-N-methylbenzamide (C260)

Isolated as a green solid (0.267 g, 86%): ¹H NMR (400 MHz, DMSO-d₆) δ7.24-7.14 (m, 2H), 7.16-7.05 (m, 2H), 6.81 (t, J=7.8 Hz, 1H), 6.54 (t,J=1.9 Hz, 1H), 6.47-6.40 (m, 1H), 6.26 (d, J=7.5 Hz, 1H), 5.10 (s, 2H),3.30 (s, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −116.06; ESIMS m/z 245([M+H]⁺).

3-Amino-N-(2-chloro-4-fluorophenyl)benzamide (C261)

Isolated as a light brown solid (0.193 g, 65%): ¹H NMR (400 MHz,DMSO-d₆) δ 9.82 (s, 1H), 7.62-7.51 (m, 2H), 7.26 (ddt, J=9.8, 7.3, 2.0Hz, 1H), 7.18-7.08 (m, 3H), 6.80-6.72 (m, 1H), 5.33 (s, 2H); ¹⁹F NMR(376 MHz, DMSO-d₆) δ −114.44; ESIMS m/z 265 ([M+H]⁺).

5-Amino-2-chloro-N-(4-fluorophenyl)-N-(prop-2-yn-1-yl)benzamide (C262)

Isolated as a brown solid (0.262 g, 100%): ¹H NMR (400 MHz, DMSO-d₆) δ7.35-7.23 (m, 2H), 7.13 (t, J=8.6 Hz, 2H), 6.87 (d, J=8.3 Hz, 1H),6.43-6.34 (m, 2H), 5.26 (s, 2H), 4.61 (d, J=2.3 Hz, 2H), 3.24 (t, J=2.3Hz, 1H). ¹⁹F NMR (376 MHz, DMSO-d₆) δ −114.03; ESIMS m/z 303 ([M+H]⁺).

5-Amino-2-chloro-N-(2,4-difluorophenyl)-N-(prop-2-yn-1-yl)benzamide(C263)

Isolated as a brown solid (0.249 g, 96%): ¹H NMR (400 MHz, DMSO-d₆) δrotamers 7.67-7.40 (m, 1H), 7.38-7.13 (m, 1H), 7.11-6.80 (m, 2H),6.75-6.25 (m, 2H), 5.32 (s, 2H), 4.76-4.35 (m, 2H), 3.24 (s, 1H). ¹⁹FNMR (376 MHz, DMSO-d₆) δ −108.53, −114.00; ESIMS m/z 321 ([M+H]⁺).

5-Amino-2-chloro-N-(4-(oxazol-2-yl)phenyl)benzamide (C264)

Isolated as a brown solid (0.185 g, 86%): mp 227° C. (dec); ¹H NMR (400MHz, DMSO-d₆) δ 10.66 (s, 1H), 8.19 (d, J=0.8 Hz, 1H), 8.02-7.92 (m,2H), 7.93-7.85 (m, 2H), 7.36 (d, J=0.8 Hz, 1H), 7.15 (d, J=8.6 Hz, 1H),6.72 (d, J=2.7 Hz, 1H), 6.67 (dd, J=8.6, 2.8 Hz, 1H), 5.50 (s, 2H);ESIMS m/z 312 ([M−H]⁻).

5-Amino-2-chloro-N-(3-fluoro-4-(trifluoromethyl)phenyl)benzamide (C265)

Isolated as a pale brown solid (0.149 g, 49%): ¹H NMR (400 MHz,Acetone-d₆) δ 9.67 (s, 1H), 8.31 (d, J=6.3 Hz, 1H), 8.10 (d, J=8.3 Hz,1H), 7.43 (t, J=9.6 Hz, 1H), 7.14 (d, J=8.6 Hz, 1H), 6.90-6.85 (m, 1H),6.77 (d, J=8.8 Hz, 1H), 5.04 (s, 2H); ¹⁹F NMR (376 MHz, Acetone-d₆) δ−62.06 (d, J=13.0 Hz), −122.83 (q, J=13.2 Hz); ESIMS m/z 331 ([M−H]⁻).

5-Amino-2-chloro-N-(3-(trifluoromethyl)phenyl)benzamide (C266)

Isolated as an orange gum (0.270 g, 74%): ¹H NMR (400 MHz, Acetone-d₆) δ9.65 (s, 1H), 8.32 (s, 1H), 8.03 (d, J=8.0 Hz, 1H), 7.61 (t, J=8.0 Hz,1H), 7.49-7.44 (m, 1H), 7.14 (d, J=8.6 Hz, 1H), 6.88 (d, J=2.8 Hz, 1H),6.77 (dd, J=8.6, 2.8 Hz, 1H), 5.04 (s, 2H); ¹⁹F NMR (376 MHz,Acetone-d₆) δ −63.28; ESIMS m/z 315 ([M−H]⁻).

5-Amino-2-chloro-N-(5-(trifluoromethyl)-1H-pyrazol-3-yl)benzamide (C267)

Isolated as a pale yellow/brown solid (0.104 g, 64%): ¹H NMR (400 MHz,DMSO-d₆) δ 13.47 (s, 1H), 11.36 (s, 1H), 7.16 (d, J=8.5 Hz, 1H), 6.72(d, J=2.7 Hz, 1H), 6.68 (dd, J=8.6, 2.8 Hz, 1H), 6.39 (s, 1H), 5.54 (s,2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ rotamers −57.81, −60.90, −61.08; ESIMSm/z 303 ([M−H]⁻).

N-(4-(1H-Pyrazol-1-yl)phenyl)-5-amino-2-chlorobenzamide (C268)

Isolated as a pale yellow/brown solid (0.231 g, 86%): mp 50-81° C.; ¹HNMR (400 MHz, DMSO-d₆) δ 10.52 (d, J=10.7 Hz, 1H), 8.44 (d, J=2.5 Hz,1H), 7.88-7.76 (m, 4H), 7.72 (d, J=1.8 Hz, 1H), 7.14 (d, J=8.6 Hz, 1H),6.72 (d, J=2.8 Hz, 1H), 6.66 (dd, J=8.6, 2.7 Hz, 1H), 6.53 (t, J=2.1 Hz,1H), 5.49 (s, 2H); ESIMS m/z 311 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 24:

5-Amino-2-ethyl-N-(4-fluorophenyl)benzamide (C269)

Isolated as a white solid (0.107 g, 75%): mp 129-131° C.; ¹H NMR (400MHz, DMSO) δ 10.27 (s, 1H), 7.75 (dd, J=9.1, 5.1 Hz, 2H), 7.20-7.11 (m,2H), 6.95 (d, J=8.3 Hz, 1H), 6.65-6.54 (m, 2H), 5.09 (s, 2H), 2.54 (dd,J=14.9, 7.4 Hz, 2H), 1.07 (t, J=7.5 Hz, 3H); ESIMS m/z 259 ([M+H]⁺).

tert-Butyl (4-(3-aminenzamido)-3-methylphenyl)carbamate (C270)

Isolated as a light brown foam (10 g, 91%): mp 143-161° C.; ¹H NMR (400MHz, DMSO-d₆) δ 9.96 (d, J=2.9 Hz, 1H), 9.32 (s, 1H), 7.95 (d, J=7.3 Hz,1H), 7.85 (s, 1H), 7.59 (td, J=7.8, 1.9 Hz, 1H), 7.55-7.47 (m, 1H),7.43-7.37 (m, 1H), 7.27 (dd, J=8.5, 2.4 Hz, 1H), 7.17 (d, J=8.5 Hz, 1H),2.17 (s, 3H), 1.48 (s, 9H) (NH₂ not observed); ESIMS m/z 342 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 28:

N-(4-Acetamido-2-fluorophenyl)-2-chloro-5-nitrobenzamide (C271)

Isolated as a white solid (0.780 g, 83%): ¹H NMR (400 MHz, DMSO-d₆) δ10.46 (s, 1H), 10.18 (s, 1H), 8.43 (d, J=2.8 Hz, 1H), 8.33 (dd, J=8.8,2.8 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.80-7.68 (m, 2H), 7.33-7.23 (m,1H), 2.06 (s, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −121.16; ESIMS m/z 352([M+H]⁺).

2-Chloro-N-(2-cyano-4-fluorophenyl)-5-nitrobenzamide (C272)

Isolated as a white solid (0.439 g, 55%): ¹H NMR (400 MHz, DMSO-d₆) δ11.06 (s, 1H), 8.52 (d, J=2.8 Hz, 1H), 8.38 (dd, J=8.8, 2.8 Hz, 1H),8.02-7.86 (m, 2H), 7.83-7.61 (m, 2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ−113.90; ESIMS m/z 320 ([M+H]⁺).

2-Chloro-5-nitro-N-(2,3,4-trifluorophenyl)benzamide (C273)

Isolated as a white solid (0.562 g, 69%): ¹H NMR (400 MHz, DMSO-d₆) δ10.80 (s, 1H), 8.50 (d, J=2.8 Hz, 1H), 8.36 (dd, J=8.8, 2.8 Hz, 1H),7.90 (d, J=8.8 Hz, 1H), 7.68 (dtt, J=12.3, 5.4, 2.6 Hz, 1H), 7.40 (tdd,J=10.2, 8.2, 2.3 Hz, 1H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −138.38 (dd,J=22.2, 4.4 Hz), −141.64 (dd, J=21.1, 4.4 Hz), −160.33 (t, J=21.6 Hz);ESIMS m/z 329 ([M−H]⁻).

2-Chloro-N-(2-cyanophenyl)-5-nitrobenzamide (C274)

Isolated as a white solid (0.315 g, 42%): ¹H NMR (400 MHz, DMSO-d₆) δ11.06 (s, 1H), 8.50 (d, J=2.8 Hz, 1H), 8.38 (dd, J=8.8, 2.8 Hz, 1H),7.99-7.87 (m, 2H), 7.86-7.69 (m, 2H), 7.48 (td, J=7.6, 1.3 Hz, 1H); ¹³CNMR (101 MHz, DMSO-d₆) δ 163.44, 146.08, 139.08, 137.21, 136.72, 133.95,133.38, 131.48, 126.81, 126.43, 126.06, 123.98, 116.55, 108.30; ESIMSm/z 302 ([M+H]⁺).

N-(4-Acetamido-2-methylphenyl)-2-chloro-5-nitrobenzamide (C275)

Isolated as a white foam (0.365 g, 53%): ¹H NMR (400 MHz DMSO-d₆) δ10.09 (s, 1H), 9.92 (s, 1H), 8.45 (d, J=2.7 Hz, 1H), 8.33 (dd, J=8.8,2.8 Hz, 1H), 7.89 (d, J=8.8 Hz, 1H), 7.49 (d, J=2.2 Hz, 1H), 7.46-7.36(m, 2H), 2.26 (s, 3H), 2.04 (s, 3H); IR (thin film) 3245, 1656, 1540,1352 cm⁻¹; ESIMS m/z 346 ([M−H]⁻).

tert-Butyl(4-chloro-3-((4-fluorophenyl)carbamoyl)phenyl)(methyl)carbamate (C276)

Isolated as a white foam (0.371 g, 93%): ¹H NMR (400 MHz, CDCl₃) δ 7.95(s, 1H), 7.68 (d, J=2.6 Hz, 1H), 7.65-7.58 (m, 2H), 7.40 (d, J=8.7 Hz,1H), 7.35 (dd, J=8.7, 2.6 Hz, 1H), 7.13-7.03 (m, 2H), 3.28 (s, 3H), 1.48(s, 9H); ¹⁹F NMR (376 MHz, CDCl₃) δ −117.08; ESIMS m/z 377 ([M−H]⁻).

2-Chloro-N-(4-iodophenyl)-5-nitrobenzamide (C277)

Isolated as a white solid (0.330 g, 55%): ¹H NMR (400 MHz, DMSO-d₆) δ10.81 (s, 1H), 8.49 (d, J=2.8 Hz, 1H), 8.34 (dd, J=8.8, 2.8 Hz, 1H),7.90 (d, J=8.8 Hz, 1H), 7.78-7.68 (m, 2H), 7.60-7.48 (m, 2H); IR (thinfilm) 3234, 1657, 1521 cm⁻¹; ESIMS m/z 403 ([M+H]⁺).

2-Chloro-N-(3-iodophenyl)-5-nitrobenzamide (C278)

Isolated as a white solid (0.340 g, 57%): ¹H NMR (400 MHz, DMSO-d₆) δ10.81 (s, 1H), 8.50 (d, J=2.7 Hz, 1H), 8.35 (dd, J=8.8, 2.8 Hz, 1H),8.21 (t, J=1.9 Hz, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.63 (ddd, J=8.1, 2.0,0.9 Hz, 1H), 7.52 (ddd, J=7.9, 1.7, 0.9 Hz, 1H), 7.19 (t, J=8.0 Hz, 1H);IR (thin film) 3257, 1653, 1521 cm⁻¹; ESIMS m/z 403 ([M+H]⁺).

2-Chloro-N-(2-fluoro-4-iodophenyl)-5-nitrobenzamide (C279)

Isolated as a white solid (0.370 g, 59%): ¹H NMR (300 MHz, DMSO-d₆) δ10.66 (s, 1H), 8.47 (d, J=2.7 Hz, 1H), 8.34 (dd, J=8.8, 2.8 Hz, 1H),7.88 (d, J=8.8 Hz, 1H), 7.77 (t, J=8.3 Hz, 2H), 7.62 (d, J=8.4 Hz, 1H);¹⁹F NMR (376 MHz, DMSO-d₆) δ −120.54; ESIMS m/z 421 ([M+H]⁺).

2-Chloro-N-(3-fluoro-4-iodophenyl)-5-nitrobenzamide (C280)

Isolated as a white solid (0.320 g, 51%): ¹H NMR (300 MHz, DMSO-d₆) δ11.02 (s, 1H), 8.52 (d, J=2.7 Hz, 1H), 8.36 (dd, J=8.8, 2.8 Hz, 1H),7.91 (d, J=8.8 Hz, 1H), 7.84 (dd, J=8.6, 7.4 Hz, 1H), 7.74 (dd, J=10.5,2.3 Hz, 1H), 7.29 (dd, J=8.7, 2.3 Hz, 1H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ−93.69; ESIMS m/z 421 ([M+H]⁺).

tert-Butyl(4-(2-chloro-5-nitrobenzamido)-3-methylphenyl)(methyl)carbamate (C281)

Isolated as a yellow foam (2.27 g, 60%): ¹H NMR (300 MHz, DMSO-d₆) δ10.16 (s, 1H), 8.49 (d, J=2.7 Hz, 1H), 8.34 (dd, J=8.8, 2.8 Hz, 1H),7.90 (d, J=8.8 Hz, 1H), 7.46 (d, J=8.4 Hz, 1H), 7.19 (d, J=2.5 Hz, 1H),7.14 (dd, J=8.4, 2.6 Hz, 1H), 3.18 (s, 3H), 2.28 (s, 3H), 1.41 (s, 9H);ESIMS m/z 418 ([M−H]⁻).

tert-Butyl (4-(2-chloro-5-nitrobenzamido)-3-methylphenyl)carbamate(C282)

Isolated as a yellow solid (2.19 g, 67%): mp 195-200° C.; ¹H NMR (300MHz, DMSO-d₆) δ 10.06 (s, 1H), 9.34 (s, 1H), 8.45 (d, J=2.7 Hz, 1H),8.33 (dd, J=8.8, 2.8 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.43-7.24 (m, 3H),2.24 (s, 3H), 1.48 (s, 9H); ESIMS m/z 404 ([M−H]⁻).

N-(2-Cyano-4-fluorophenyl)-3-nitrobenzamide (C283)

Isolated as a white solid (0.316 g, 62%): ¹H NMR (400 MHz, DMSO-d₆) δ11.02 (s, 1H), 8.84 (t, J=2.0 Hz, 1H), 8.58-8.31 (m, 2H), 8.03-7.82 (m,2H), 7.76-7.54 (m, 2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −114.32; ESIMS m/z286 ([M+H]⁺).

N-(4-Fluoro-2-methylphenyl)-3-nitrobenzamide (C284)

Isolated as a purple solid (0.348 g, 71%): ¹H NMR (400 MHz, DMSO-d₆) δ10.29 (s, 1H), 8.80 (t, J=2.0 Hz, 1H), 8.52-8.34 (m, 2H), 7.85 (t, J=8.0Hz, 1H), 7.36 (dd, J=8.7, 5.6 Hz, 1H), 7.18 (dd, J=9.7, 3.0 Hz, 1H),7.08 (td, J=8.6, 3.0 Hz, 1H), 2.24 (s, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ−116.58; ESIMS m/z 275 ([M+H]⁺).

N-(4-Fluorophenyl)-N-methyl-3-nitrobenzamide (C285)

Isolated as a dark oil (0.335 g, 68%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.14(d, J=9.3 Hz, 2H), 7.67 (d, J=7.6 Hz, 1H), 7.54 (t, J=7.8 Hz, 1H), 7.35(dd, J=8.7, 5.0 Hz, 2H), 7.13 (t, J=8.8 Hz, 2H), 3.39 (s, 3H); ¹⁹F NMR(376 MHz, DMSO-d₆) δ −114.74; ESIMS m/z 275 ([M+H]⁺).

N-(2-Chloro-4-fluorophenyl)-3-nitrobenzamide (C286)

Isolated as a tan solid (0.230 g, 44%): ¹H NMR (400 MHz, DMSO-d₆) δ10.55 (s, 1H), 8.81 (t, J=2.0 Hz, 1H), 8.61-8.26 (m, 2H), 7.86 (t, J=8.0Hz, 1H), 7.71-7.53 (m, 2H), 7.31 (td, J=8.5, 2.9 Hz, 1H); ¹⁹F NMR (376MHz, DMSO-d₆) δ −113.58; ESIMS m/z 295 ([M+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(2-chloro-5-nitrobenzamido)-2,4-difluorophenyl)carbamate(C287)

Isolated as a yellow oil (5.2 g, 66%): ¹H NMR (400 MHz, DMSO-d₆) δ 10.9(s, 1H), 8.51 (d, J=2.7 Hz, 1H), 8.35 (dd, J=8.8, 2.8 Hz, 1H), 7.97-7.79(m, 2H), 7.30 (td, J=9.3, 1.7 Hz, 1H), 1.41 (s, 18H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −123.43, −127.02 (d, J=2.0 Hz); ESIMS m/z 526 ([M−H]⁻).

2-Chloro-N-(4-fluoro-2-(trifluoromethyl)phenyl)-5-nitrobenzamide (C288)

Isolated as an orange foam (0.120 g, 10%): ¹H NMR (400 MHz, Acetone-d₆)59.57 (s, 1H), 8.49 (d, J=2.8 Hz, 1H), 8.36 (dd, J=8.8, 2.7 Hz, 1H),7.96 (dd, J=8.8, 5.1 Hz, 1H), 7.85 (d, J=8.8 Hz, 1H), 7.65-7.53 (m, 2H);¹⁹F NMR (376 MHz, Acetone-d₆) δ −61.54, −114.26. ESIMS m/z 360 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 30:

2-Chloro-5-nitro-N-(4-(trifluoromethyl)thiazol-2-yl)benzamide (C289)

Isolated as a yellow glass (0.181 g, 52%): ¹H NMR (400 MHz, DMSO-d₆) δ13.41 (s, 1H), 8.63 (d, J=2.8 Hz, 1H), 8.39 (dd, J=8.9, 2.8 Hz, 1H),8.12 (d, J=1.1 Hz, 1H), 7.92 (d, J=8.9 Hz, 1H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −62.92; ESIMS m/z 352 ([M+H]⁺).

2-Chloro-N-(5-chloropyridin-2-yl)-5-nitrobenzamide (C290)

Isolated as a white solid (0.110 g, 36%): ¹H NMR (400 MHz, DMSO-d₆) δ11.55 (s, 1H), 8.50 (d, J=2.7 Hz, 1H), 8.38 (d, J=5.4 Hz, 1H), 8.34 (dd,J=8.8, 2.8 Hz, 1H), 8.28 (t, J=2.6 Hz, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.37(dd, J=5.4, 1.9 Hz, 1H); IR (thin film) 3103, 1778, 1688, 1566, 1524cm⁻¹; ESIMS m/z 312 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 31:

2-Chloro-N-(4-fluoro-3-(trifluoromethyl)phenyl)-5-nitrobenzamide (C291)

Isolated as an off-white solid (0.270 g, 55%): mp 192-202° C.; ¹H NMR(400 MHz, Acetone-d₆) δ 10.15 (s, 1H), 8.55 (d, J=2.8 Hz, 1H), 8.35 (dd,J=8.8, 2.8 Hz, 1H), 8.26 (dd, J=6.4, 2.7 Hz, 1H), 8.10-8.01 (m, 1H),7.84 (d, J=8.8 Hz, 1H), 7.44 (t, J=9.6 Hz, 1H); ¹⁹F NMR (376 MHz,Acetone-d₆) δ −62.03 (d, J=12.9 Hz), −121.52 (q, J=12.9 Hz).

2-Chloro-5-nitro-N-(3-(trifluoromethyl)phenyl)benzamide (C292)

Isolated as a brown solid (0.350 g, 76%): ¹H NMR (400 MHz, Acetone-d₆) δ10.14-10.09 (m, 1H), 8.57 (d, J=2.8 Hz, 1H), 8.35 (dd, J=8.8, 2.8 Hz,1H), 8.28 (d, J=4.0 Hz, 0H), 8.28 (s, 1H), 7.99 (dt, J=8.2, 1.3 Hz, 1H),7.84 (d, J=8.8 Hz, 1H), 7.63 (t, J=8.0 Hz, 1H), 7.52 (ddt, J=7.8, 1.8,0.9 Hz, 1H); ¹⁹F NMR (376 MHz, Acetone) δ −63.25; ESIMS m/z 342([M−H]⁻).

N-(4-(1H-Pyrazol-1-yl)phenyl)-2-chloro-5-nitrobenzamide (C293)

Isolated as a light brown solid (0.270 g, 52%): mp 200-205° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 10.84 (s, 1H), 8.51 (d, J=2.8 Hz, 1H), 8.46 (d,J=2.4 Hz, 1H), 8.35 (dd, J=8.8, 2.8 Hz, 1H), 7.91 (d, J=8.8 Hz, 1H),7.90-7.78 (m, 4H), 7.74 (d, J=1.7 Hz, 1H), 6.58-6.52 (m, 1H); ESIMS m/z341 ([M−H]⁻).

2-Chloro-5-nitro-N-(4-(oxazol-2-yl)phenyl)benzamide (C294)

Isolated as a pink foam (0.233 g, 44%): mp 192-194° C.; ¹H NMR (400 MHz,DMSO-d₆) δ 10.99 (s, 1H), 8.53 (d, J=2.8 Hz, 1H), 8.36 (dd, J=8.9, 2.8Hz, 1H), 8.21 (d, J=0.8 Hz, 1H), 8.06-7.95 (m, 2H), 7.96-7.84 (m, 3H),7.37 (d, J=0.8 Hz, 1H); ESIMS m/z 342 ([M−H]⁻).

2-Chloro-5-nitro-N-(5-(trifluoromethyl)-1H-pyrazol-3-yl)benzamide (C295)

Isolated as an off-white solid (0.170 g, 37%): ¹H NMR (400 MHz, DMSO-d₆)δ13.63 (s, 1H), 11.71 (s, 1H), 8.52 (s, 1H), 8.37 (dd, J=8.8, 2.8 Hz,1H), 7.91 (d, J=8.9 Hz, 1H), 6.54 (s, 1H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ−60.91; ESIMS m/z 332 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 32:

2-Chloro-N-(4-fluoro-2-methylphenyl)-N-methyl-5-nitrobenzamide (C296)

Isolated as a white solid (0.550 g, 100%): ¹H NMR (400 MHz, CDCl₃) δ7.99 (dd, J=8.7, 2.7 Hz, 1H), 7.95 (d, J=2.6 Hz, 1H), 7.43 (d, J=8.7 Hz,1H), 7.16 (dd, J=8.7, 5.3 Hz, 1H), 6.85 (dd, J=9.0, 2.9 Hz, 1H), 6.73(td, J=8.2, 3.0 Hz, 1H), 3.40 (s, 3H), 2.37 (s, 3H); ¹⁹F NMR (376 MHz,CDCl₃) δ −112.14; ESIMS m/z 323 ([M+H]⁺).

tert-Butyl(4-(2-chloro-N-methyl-5-nitrobenzamido)-3-methylphenyl)(methyl)carbamate(C297)

Isolated as a yellow oil (0.240 g, 99%): ¹H NMR (300 MHz, DMSO-d₆) δrotamers 8.33 (dd, J=8.8, 2.8 Hz, 0.3H), 8.17 (d, J=2.7 Hz, 0.7H), 8.05(dd, J=8.8, 2.8 Hz, 0.7H), 7.99-7.88 (m, 0.6H), 7.73-7.62 (m, 0.7H),7.31-7.22 (m, 1H), 7.09 (d, J=2.6 Hz, 1H), 6.95 (dd, J=8.4, 2.6 Hz, 1H),3.30 (s, 2H), 3.21 (s, 1H), 3.05 (d, J=1.5 Hz, 3H), 2.30 (s, 3H), 1.43(s, 3H), 1.23 (s, 6H); IR (thin film) 2925, 1697, 1653, 1574 cm⁻¹;HRMS-ESI (m/z) [M+H]⁺ calcd for C₂₁H₂₄CN₃O₅, 434.1477; found, 434.1474.

2-Chloro-N-(2-cyano-4-fluorophenyl)-N-methyl-5-nitrobenzamide (C298)

Isolated as a yellow solid (0.211 g, 91%): ¹H NMR (400 MHz, DMSO-d₆) δ8.51-8.46 (m, 1H), 8.38 (d, J=2.8 Hz, 1H), 8.04 (dd, J=8.4, 2.9 Hz, 1H),7.95 (d, J=8.9 Hz, 1H), 7.92-7.86 (m, 1H), 7.80 (td, J=8.6, 2.9 Hz, 1H),3.19 (s, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −111.69; ESIMS m/z 334([M+H]⁺).

2-Chloro-N-(4-fluorophenyl)-5-nitro-N-(prop-2-yn-1-yl)benzamide (C299)

Isolated as a light brown solid (0.296 g, 94%): ¹H NMR (400 MHz,DMSO-d₆) δ 8.37 (d, J=2.8 Hz, 1H), 8.08 (dd, J=8.8, 2.8 Hz, 1H), 7.63(d, J=8.8 Hz, 1H), 7.49-7.40 (m, 2H), 7.20-7.08 (m, 2H), 4.69 (s, 2H),3.30 (t, J=2.5 Hz, 1H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −112.89; ESIMS m/z333 ([M+H]⁺).

2-Chloro-N-(2,4-difluorophenyl)-5-nitro-N-(prop-2-yn-1-yl)benzamide(C300)

Isolated as a light brown oil (0.293 g, 89%): ¹H NMR (400 MHz, DMSO-d₆)δ 8.21 (d, J=2.6 Hz, 1H), 8.13 (dd, J=8.8, 2.8 Hz, 1H), 7.73-7.65 (m,2H), 7.29 (ddd, J=10.4, 9.0, 2.8 Hz, 1H), 7.14-7.02 (m, 1H), 4.69 (d,J=2.5 Hz, 2H), 3.30 (t, J=2.5 Hz, 1H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ−107.45, −114.08 (d, J=8.4 Hz); ESIMS m/z 351 ([M+H]⁺).

Example 36: Preparation oftrans-2,2-dibromo-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylic acid(C301)

To a solution oftrans-2,2-dibromo-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde(C305) (1.67 g, 4.48 mmol) in acetonitrile (15.36 mL) and water (2.5 mL)was added sodium hydrogen sulfite (3.26 g, 31.36 mmol). The resultantsolution was cooled to 0° C., sodium chlorite (3.54 g, 17.92 mmol) wasadded slowly, and the solution was stirred for overnight while slowlywarming to room temperature. The mixture was then diluted with aqueoushydrochloric acid solution (1 N) until the pH was equal to or less than3. The mixture was then repeatedly extracted with ethyl acetate. Thecombined organic extracts were dried over sodium sulfate, filtered andconcentrated under vacuum. Purification of the crude solid by flashcolumn chromatography with 0-100% ethyl acetate/hexanes as eluentprovided the title compound as a light brown solid (0.91 g, 52%): ¹H NMR(400 MHz, CDCl₃) δ 7.36 (t, J=1.9 Hz, 1H), 7.17 (dd, J=1.9, 0.8 Hz, 2H),3.39 (d, J=8.2 Hz, 1H), 2.91 (d, J=8.2 Hz, 1H); ¹³C NMR (101 MHz, CDCl³)δ 172.15, 136.91, 135.25, 128.64, 127.29, 40.29, 37.32, 26.57; ESIMS m/z386 ([M−H]⁻).

Example 37: Preparation oftrans-2-chloro-3-(3,5-dichlorophenyl)-cyclopropane-1-carboxylic acid(C302)

Thionyl chloride (2.55 g, 35.0 mmol) was added dropwise to a stirredsolution oftrans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxylic acid(C1) (2.10 g, 7.0 mmol) in anhydrous methanol (20 mL) at roomtemperature. Upon completion of the addition, the resulting solution wasstirred for another 2 hours, then concentrated under vacuum on a rotaryevaporator to afford a gold oil. The crude product was diluted withwater (100 mL), and the aqueous mixture was extracted with ethyl acetate(3×50 mL). The combined organic extracts were washed with water andbrine, dried over anhydrous magnesium sulfate, filtered, andconcentrated under reduced pressure on a rotary evaporator to givemethyl 2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylate(2.168 g, 94%) as a clear colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 7.34(s, 1H), 7.16 (dd, J=1.9, 0.7 Hz, 2H), 3.85 (s, 3H), 3.45-3.37 (m, 1H),2.84 (d, J=8.3 Hz, 1H).

t-Butylmagnesium chloride (1M in tetrahydrofuran (THF), 8.0 mL, 7.96mmol) was added dropwise to a stirred solution of methyl2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylate (1.0 g,3.18 mmol). Hexamethylphosphoramide (0.571 g, 3.18 mmol) and[1,2-bis(diphenylphosphino)ethane]dichlorocobalt(II) (0.084 g, 0.159mmol) in anhydrous THF (15 mL) at 5° C. Upon completion of the addition,the reaction was warmed to room temperature, stirred for another 30minutes, and quenched with aqueous hydrochloric acid (1 N, 10 mL). Theaqueous mixture was extracted with ethyl ether (3×50 mL). The combinedorganic extracts were washed with water and brine, dried over anhydrousmagnesium sulfate, filtered, and concentrated under reduced pressure ona rotary evaporator. The resulting crude product was purified by silicagel flash chromatography (ethyl acetate/hexanes mobile phase) to givemethyl 2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylate (0.425g, 45.3%) as a yellow oil: GC-MS analysis showed a 1:1 mixture ofdiastereomers.

Powdered lithium hydroxide monohydrate (0.067 g, 1.61 mmol) was added inone portion to a stirred solution of methyl2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylate (0.41 g, 1.47mmol) in THF (5 mL) and water (1 mL). After stirring for 2 days at roomtemperature, the resulting pale yellow solution was made acidic (pH 2)with aqueous hydrochloric acid (1 N) and extracted with ethyl acetate(3×50 mL). The combined organic extracts were washed with water andbrine, dried over anhydrous magnesium sulfate, filtered, andconcentrated under reduced pressure on a rotary evaporator. Theresulting crude product was purified by C-18 flash chromatography(acetonitrile/water mobile phase) to give2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylic acid (0.270 g,65.9%) as a white solid. 400 MHz ¹H NMR spectral analysis showed a 1:1mixture of diastereomers: ¹H NMR (400 MHz, Acetone-d₆) δ 9.11 (s, 1H),7.43-7.32 (m, 2H), 7.32-7.26 (m, 1H), 4.02-3.76 (m, 1H), 3.19-2.96 (m,1H), 2.84-2.56 (m, 1H); ESIMS m/z 264 ([M−H]⁻).

Example 38: Preparation oftrans-2,2-dichloro-3-methyl-3-(4-(trifluoromethoxy)phenyl)cyclopropane-1-carboxylicacid (C303)

A solution oftrans-(2,2-dichloro-3-methyl-3-(4-(trifluoromethoxy)phenyl)cyclopropyl)methanol(C323) (2.4 g, 7.62 mmol) in acetone (20 mL) was added dropwise underrapid stirring to a solution of Jones Reagent (9.7 mL, 4.11 g, 19.04mmol) in acetone (20 mL) at 2° C. The reaction mixture was allowed towarm slowly to ambient temperature under nitrogen over 14 hours. Themixture was cooled in a freezing salt (salt-ice) bath before addingisopropyl alcohol (20 mL) dropwise over 1 hour. The resultant suspensionwas warmed to ambient temperature over 3 hours and filtered to removechromium salts, which were washed thoroughly with acetone (100 mL). Thefiltrate was concentrated under reduced pressure. The residue wassuspended in water (100 mL) and extracted with ethyl acetate (3×70 mL).The combined organic extracts were washed with water (100 mL) and brine(60 mL), dried over magnesium sulfate, and concentrated under reducedpressure. The residue was taken up in ethyl ether (100 mL) and extractedwith dilute sodium hydroxide solution (0.2 N, 3×40 mL). The combinedaqueous extracts were cooled in an ice bath, acidified to pH 4 usingdilute hydrochloric acid and extracted with ethyl acetate (3×50 mL). Thecombined organic extracts were washed with water (100 mL) and brine (80mL), dried over magnesium sulfate, and concentrated under reducedpressure. The residue was dried in vacuo at 44° C. for 14 hours to leavea yellow solid (1.93 g, 77%): mp 99-101° C.; ¹H NMR (400 MHz, CDCl₃) δ7.36 (dt, J=9.1, 2.3 Hz, 2H), 7.24 (br d, J=8.8 Hz, 2H), 2.79 (s, 1H),1.77 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −57.85; ¹³C NMR (101 MHz,CDCl₃) δ 171.49, 148.63, 139.63, 129.69, 124.25, 121.69, 121.19, 119.13,116.57, 66.23, 42.85, 38.91, 20.39; ESIMS m/z 327.99 ([M−H]⁻); IR (thinfilm) 1714.9, 1253.3, 1206.0, 1160.3 cm⁻¹.

Example 39: Preparation oftrans-2,2-dichloro-3-(4-nitrophenyl)cyclopropyl)methanol (C304)

To a stirred solution of(E)-2-((3-(4-nitrophenyl)allyl)oxy)tetrahydro-2H-pyran (C322) (0.5 g,1.899 mmol) and tetrabutylammonium hexafluorophosphate(V) (0.037 g,0.095 mmol) in chloroform (6.33 mL) was added powdered sodium hydroxide(1.139 g, 28.5 mmol), and the reaction mixture was vigorously stirred atroom temperature for 18 hours. The reaction mixture was diluted withwater and dichloromethane, and the layers were separated. The organiclayer was concentrated and purified by flash column chromatographygiving2-((trans-2,2-dichloro-3-(4-nitrophenyl)cyclopropyl)methoxy)-tetrahydro-2H-pyranas a mixture of diastereomers. The mixture was dissolved in methanol (10mL). To the methanol solution was added p-toluenesulfonic acid (0.020 g,0.107 mmol), and the reaction mixture was stirred at room temperaturefor 18 hours. The reaction mixture was quenched with saturated sodiumbicarbonate and extracted with ethyl acetate (2×). The combined organiclayers were dried over sodium sulfate, filtered, and concentrated givingthe title compound as a yellow oil (310 mg, 53% over 2 steps): ¹H NMR(400 MHz, CDCl₃) δ 8.22 (d, J=8.7 Hz, 2H), 7.52-7.34 (m, 2H), 4.10 (ddd,J=12.4, 7.2, 5.3 Hz, 1H), 3.95 (ddd, J=12.0, 8.0, 5.0 Hz, 1H), 2.78 (d,J=8.3 Hz, 1H), 2.37 (td, J=8.2, 5.4 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ147.43, 141.42, 129.77, 123.59, 63.74, 62.25, 38.50, 37.04; IR (thinfilm) 1598, 1514, 1345, 1046 cm⁻¹; HRMS-ESI (m/z) [M+Na]⁺ calcd forC₁₀H₉Cl₂NO₃Na, 283.9852; found, 283.9844.

Example 40: Preparation oftrans-2,2-dibromo-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde(C305)

To a solution of (E)-1,3-dichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene(C449) (500 mg, 1.817 mmol) in bromoform (12.1 mL) were addedtetrabutylammonium hexafluorophosphate(V) (70.4 mg, 0.182 mmol) followedby solid sodium hydroxide (Careful! Add slowly! 1454 mg, 36.3 mmol). Themixture was heated to 90° C. while stirring overnight. The mixture wasthen diluted with dichloromethane and water and extracted withadditional dichloromethane. The organic layer was then dried over sodiumsulfate and concentrated. Purification by flash column chromatographyusing 0-100% ethyl acetate/hexanes as eluent provided the resultingelutant, which was then dissolved in acetone (4 mL) and aqueoushydrochloric acid (2 N, 1 mL, 2 mmol). The mixture was stirredovernight. The mixture was diluted with saturated sodium bicarbonatesolution until the pH of the solution was greater than 7. The mixturewas then extracted with diethyl ether and ethyl acetate, and thecombined organic layers were dried over sodium sulfate and concentratedproviding the dark brown product (0.03 g, 4%): ¹H NMR (400 MHz, CDCl₃) δ9.48 (d, J=4.0 Hz, ¹H), 7.37 (t, J=1.9 Hz, 1H), 7.17 (dd, J=1.9, 0.7 Hz,2H), 3.60-3.36 (m, 1H), 2.90 (dd, J=7.9, 4.0 Hz, 1H); ¹³C NMR (101 MHz,CDCl₃) δ 194.74, 136.55, 135.31, 128.76, 127.34, 42.34, 39.84, 26.05;ESIMS m/z 343 ([M−CHO]⁻).

Example 41: Preparation of1-bromo-2-chloro-4-(trans-2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene(C306)

To a stirred solution of (E)-1-bromo-2-chloro-4-(4-methoxystyryl)benzene(C312) (0.38 g, 1.174 mmol) and tetrabutylammoniumhexafluorophosphate(V) (0.045 g, 0.117 mmol) in chloroform (5.61 g, 3.77mL, 47.0 mmol) was added aqueous sodium hydroxide (50%, 2.348 g, 29.4mmol), and the resulting mixture was stirred vigorously at roomtemperature for 40 hours. The reaction mixture was diluted with waterand was extracted with dichloromethane. The combined organic layers weredried over sodium sulfate, filtered, and concentrated. Purification byflash column chromatography using 0-10% ethyl acetate/hexanes as eluentprovided the title compound as a colorless oil (0.362 g, 72%): ¹H NMR(400 MHz, CDCl₃) δ 7.62 (d, J=8.3 Hz, 1H), 7.46 (d, J=2.0 Hz, 1H),7.29-7.23 (m, 2H), 7.13 (dd, J=8.3, 2.1 Hz, 1H), 6.93 (d, J=8.7 Hz, 2H),3.83 (s, 3H), 3.12 (d, J=8.7 Hz, 1H), 3.07 (d, J=8.7 Hz, 1H); ¹³C NMR(101 MHz, CDCl₃) δ 159.43, 135.68, 134.63, 133.68, 130.80, 129.90,128.49, 125.81, 121.83, 114.01, 64.86, 55.33, 39.54, 38.85; IR (thinfilm) 3356 (br), 3002, 2835, 1514, 1248 cm⁻¹.

The following compounds were prepared in like manner to the procedureoutlined in Example 41:

2-bromo-1-chloro-4-(trans-2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene(C307)

Isolated as a thick yellow oil (1.1321 g, 74.4%): ¹H NMR (400 MHz,CDCl₃) δ 7.62 (d, J=2.1 Hz, 1H), 7.46 (d, J=8.3 Hz, 1H), 7.30-7.20 (m,3H), 6.93 (d, J=8.7 Hz, 2H), 3.82 (s, 3H), 3.12 (d, J=8.8 Hz, 1H), 3.08(d, J=8.8 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 159.42, 135.02, 134.13,133.97, 130.24, 129.90, 129.01, 125.82, 122.51, 114.01, 64.98, 55.33,39.57, 38.66; IR (thin film) 3001, 2932, 2835, 1514, 1248 cm⁻¹.

1-Bromo-3-chloro-5-(trans-2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene(C308)

Isolated as a thick yellow oil (2.612 g, 83%): ¹H NMR (400 MHz, CDCl₃) δ7.49 (t, J=1.8 Hz, 1H), 7.41 (d, J=1.7 Hz, 1H), 7.30 (d, J=1.8 Hz, 1H),7.28-7.23 (m, 2H), 6.93 (d, J=8.7 Hz, 2H), 3.83 (s, 3H), 3.13 (d, J=8.7Hz, 1H), 3.08 (d, J=8.8 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 159.45,138.28, 135.18, 130.82, 130.41, 129.88, 128.00, 125.66, 122.72, 114.02,64.81, 55.32, 39.56, 38.89; IR (thin film) 3000, 2931, 2835, 1588, 1550,1513 cm⁻¹.

2-Bromo-5-(trans-2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-1,3-difluorobenzene(C309)

Isolated as a yellow solid (3.44 g, 79%): mp 104.0-109.3° C.; ¹H NMR(400 MHz, CDCl₃) δ 7.28-7.22 (m, 2H), 7.02-6.96 (m, 2H), 6.96-6.90 (m,2H), 3.83 (s, 3H), 3.12 (d, J=8.7 Hz, 1H), 3.08 (d, J=8.7 Hz, 1H); ¹³CNMR (101 MHz, CDCl₃) δ 161.10, 159.49, 129.86, 125.47, 114.04, 112.79,112.56, 112.53, 64.66, 55.33, 39.77, 39.01; ¹⁹F NMR (376 MHz, CDCl₃) δ−104.75.

2-Bromo-5-(trans-2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-1-fluoro-3-methoxybenzene(C310)

Isolated as a yellow oil (1.18 g, 76%): ¹H NMR (400 MHz, CDCl₃) δ7.30-7.26 (m, 2H), 6.96-6.91 (m, 2H), 6.80-6.74 (m, 1H), 6.70 (d, J=1.6Hz, 1H), 3.96 (s, 3H), 3.83 (s, 3H), 3.15-3.07 (m, 2H); ¹³C NMR (101MHz, CDCl₃) δ 161.20, 159.43, 136.09, 135.99, 129.91, 125.85, 114.01,109.29, 109.05, 108.20, 64.91, 56.79, 55.33, 39.59, 39.49; ¹⁹F NMR (376MHz, CDCl₃) δ −104.96.

1-Bromo-5-(trans-2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-3-fluoro-2-methoxybenzene(C311)

Isolated as a yellow oil (0.37 g, 59%); ¹H NMR (400 MHz, CDCl₃) δ7.31-7.23 (m, 3H), 6.98 (d, J=11.6 Hz, 1H), 6.96-6.90 (m, 2H), 3.92 (s,3H), 3.83 (s, 3H), 3.13 (d, J=8.8 Hz, 1H), 3.07 (d, J=8.8 Hz, 1H); ¹³CNMR (101 MHz, CDCl₃) δ 159.38, 152.57, 147.73, 129.93, 127.93, 125.93,120.63, 117.66, 117.23, 113.97, 65.40, 56.57, 55.33, 40.10, 39.59; ¹⁹FNMR (376 MHz, CDCl₃) δ −135.58.

Example 42: Preparation of(E)-1-bromo-2-chloro-4-(4-methoxystyryl)benzene (C312)

To a stirred solution of diethyl (4-methoxybenzyl)phosphonate (0.619 mL,2.73 mmol) in N,N-dimethylformamide (3 mL) at 0° C. was added a solutionof sodium methoxide (5.4 M in methanol, 0.844 mL, 4.56 mmol). A solutionof 4-bromo-3-chlorobenzaldehyde (0.5 g, 2.278 mmol) inN,N-dimethylformamide (1 mL) was added, and the reaction mixture washeated to 65° C. for 4 hours. The reaction mixture was allowed to coolto room temperature and was partitioned between water and ethyl acetate.The organic layer was dried over magnesium sulfate, filtered, andconcentrated. Purification by flash column chromatography using 0-10%ethyl acetate/hexanes as eluent provided the title compound as a yellowcrystalline solid (0.484 g, 59%): mp 77-88° C.; ¹H NMR (400 MHz, CDCl₃)δ 7.58-7.53 (m, 2H), 7.47-7.39 (m, 2H), 7.22 (dd, J=8.4, 2.1 Hz, 1H),7.06 (d, J=16.2 Hz, 1H), 6.95-6.87 (m, 2H), 6.84 (d, J=16.3 Hz, 1H),3.84 (s, 3H); EIMS m/z 324.

The following compounds were prepared in like manner to the procedureoutlined in Example 42:

(E)-2-bromo-1-chloro-4-(4-methoxystyryl)benzene (C313)

Isolated as a white solid (1.15 g, 70.2%): 87.1-92.3° C.; ¹H NMR (400MHz, CDCl₃) δ 7.71 (d, J=2.0 Hz, 1H), 7.42 (dd, J=9.5, 7.4 Hz, 2H), 7.37(s, 1H), 7.32 (dd, J=8.4, 2.1 Hz, 1H), 7.02 (d, J=16.2 Hz, 1H),6.93-6.86 (m, 2H), 6.82 (d, J=16.3 Hz, 1H), 3.83 (s, 3H); ¹³C NMR (101MHz, CDCl₃) δ 159.79, 138.01, 132.53, 131.05, 130.33, 130.17, 129.36,127.97, 126.03, 123.84, 122.71, 114.26, 55.34; EIMS m/z 324.0.

(E)-1-Bromo-3-chloro-5-(4-methoxystyryl)benzene (C314)

Isolated as a pale yellow oil (2.39 g, 77%): ¹H NMR (400 MHz, CDCl₃) δ7.48 (d, J=1.7 Hz, 1H), 7.45-7.39 (m, 2H), 7.35 (dt, J=9.6, 1.8 Hz, 2H),7.04 (d, J=16.2 Hz, 1H), 6.90 (d, J=8.8 Hz, 2H), 6.79 (d, J=16.2 Hz,1H), 3.83 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 159.95, 141.10, 135.29,131.08, 129.49, 129.11, 128.11, 127.37, 124.91, 123.61, 122.95, 114.29,55.35; EIMS m/z 324.1.

Example 43: Preparation of(E)-2-bromo-1,3-difluoro-5-(4-methoxystyryl)benzene (C315) and(E)-2-bromo-1-fluoro-3-methoxy-5-(4-methoxystyryl)benzene (C316)

To a stirred solution of diethyl (4-methoxybenzyl)phosphonate (5.54 mL,24.43 mmol) in N,N-dimethylformamide (27 mL) at 0° C. was added asolution of sodium methoxide (5.4 M in methanol, 4.52 mL, 24.43 mmol).4-Bromo-3,5-difluorobenzaldehyde (4.5 g, 20.36 mmol) inN,N-dimethylformamide (9 mL) was added, and the reaction mixture washeated to 65° C. for 1 hour. The reaction mixture was allowed to cool toroom temperature and was partitioned between water and ethyl acetate.The organic layer was dried over magnesium sulfate, filtered, andconcentrated. Purification by flash column chromatography using 0-10%ethyl acetate/hexanes as eluent provided(E)-2-bromo-1,3-difluoro-5-(4-methoxystyryl)benzene (C315) as a whitesolid (3.28 g, 47%) and(E)-2-bromo-1-fluoro-3-methoxy-5-(4-methoxystyryl)benzene (C316) as awhite solid (1.19 g, 16%). C315: mp 104.1-112.7° C.; ¹H NMR (400 MHz,CDCl₃) δ 7.48-7.41 (m, 2H), 7.10-7.02 (m, 3H), 6.94-6.88 (m, 2H), 6.82(d, J=16.2 Hz, 1H), 3.84 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −106.11;EIMS m/z 324.0. C316: mp 118.5-123.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.45(d, J=8.6 Hz, 2H), 7.06 (d, J=16.2 Hz, 1H), 6.91 (dd, J=9.1, 2.2 Hz,3H), 6.86 (d, J=16.2 Hz, 1H), 6.78 (t, J=1.5 Hz, 1H), 3.96 (s, 3H), 3.84(s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −106.15; EIMS m/z 336.0.

Example 44: Preparation of(E)-1-bromo-3-fluoro-2-methoxy-5-(4-methoxy-styryl)benzene (C317)

To a stirred solution of diethyl (4-methoxybenzyl)phosphonate (1.85 mL,8.14 mmol) in N,N-dimethylformamide (9 mL) at 0° C. was added a solutionof sodium methoxide (5.4 M in methanol, 1.38 mL, 7.47 mmol).3-Bromo-4,5-fluorobenzaldehyde (1.5 g, 6.79 mmol) inN,N-dimethylformamide (3 mL) was added, and the reaction mixture washeated to 65° C. for 2 hours. The reaction mixture was allowed to coolto room temperature and was partitioned between water and ethyl acetate.The organic layer was dried over magnesium sulfate, filtered, andconcentrated. Purification by flash column chromatography using 0-10%ethyl acetate/hexanes as eluent provided(E)-1-bromo-3-fluoro-2-methoxy-5-(4-methoxystyryl)benzene as a whitesolid (0.48 g, 20%): mp 78.0-84.8° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.47(d, J=8.7 Hz, 2H), 7.39 (d, J=12.5 Hz, 1H), 7.19 (dd, J=16.1, 1.7 Hz,1H), 7.14 (d, J=8.1 Hz, 1H), 6.94-6.89 (m, 2H), 6.86 (d, J=16.2 Hz, 1H),3.90 (s, 3H), 3.84 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −135.86; EIMS m/z336.0.

Example 45: Preparation of (E)-2-Chloro-5-(4-methoxystyryl)thiophene(C318)

5-Chlorothiophene-2-carbaldehyde (1.35 g, 9.21 mmol) and diethyl4-methoxybenzylphosphonate (1.59 mL, 9.21 mmol) were dissolved inN,N-dimethylformamide (18 mL). To this mixture was added sodiummethoxide (25% in methanol, 2.51 mL, 11.05 mmol) at room temperature.After 16 hours, the reaction mixture was diluted with water withstirring. The precipitate was collected by filtration, was washed withwater and was dried. The precipitate was dissolved in ethyl acetate, andthe solution was washed with brine. The layers were separated, and theorganic layer was dried over sodium sulfate, filtered, and concentratedto give (E)-2-chloro-5-(4-methoxystyryl)thiophene (1.550 g, 67.1%) as adark yellow powder: ¹H NMR (400 MHz, CDCl₃) δ 7.41-7.35 (m, 2H), 6.94(dd, J=16.1, 0.5 Hz, 1H), 6.91-6.83 (m, 2H), 6.81-6.70 (m, 3H), 3.82 (s,3H); ¹³C NMR (101 MHz, CDCl₃) δ 159.47, 142.09, 129.34, 128.13, 127.93,127.58, 126.63, 124.58, 119.34, 114.21, 55.32; EIMS m/z 250.

Example 46: Preparation of ethyl(E)-3-(4-(trifluoromethoxy)phenyl)but-2-enoate (C319)

Based on a procedure by Z-C Duan, X-P Hu, C Zhang and Z Zheng in OrgChem (2010) 75(23), 8319-8321. Neat ethyl 2-(diethoxyphosphoryl)acetate(10.98 g, 49 mmol) was added dropwise under nitrogen to an ice-cold,stirred suspension of 60% sodium hydride in mineral oil (1.96 g, 49mmol) in dry tetrahydrofuran (80 mL), taking care to maintain thetemperature below 3° C. The reactants were stirred for 30 minutes beforeaddition of 1-(4-(trifluoromethoxy)phenyl)ethanone (8.0 g, 39.2 mmol).The reaction mixture was allowed to warm slowly to ambient temperatureunder nitrogen to give a thick, yellow gum. Saturated aqueous ammoniumchloride (80 mL) was added dropwise under rapid stirring. This mixturewas extracted with ethyl ether (2×170 mL). The combined organic extractswas washed with water (400 mL) and brine (200 mL), dried over magnesiumsulfate, and purified by silica gel chromatography, eluting with agradient of ethyl acetate in hexane. Two closely eluting fractions wereobtained. The desired product was obtained from the faster elutingfraction as a colorless liquid (9.0 g, 84%) after drying in vacuo at 42°C. for 14 hours: ¹H NMR (400 MHz, CDCl₃) δ 7.50 (dt, J=8.9, 2.1 Hz, 2H),7.21 (dd, J=8.9, 0.9 Hz, 2H), 6.11 (d, J=1.3 Hz, 1H), 4.22 (q, J=7.1 Hz,2H), 2.56 (d, J=1.3 Hz, 3H), 1.32 (t, J=7.1 Hz, 3H); ¹³C NMR (101 MHz,CDCl₃) δ 166.58, 153.79, 149.63, 149.61, 140.82, 127.82, 124.26, 121.70,120.81, 119.14, 117.95, 116.58, 60.02, 17.95, 14.33; ¹⁹F NMR (376 MHz,CDCl₃) δ −57.82; IR (thin film) 1712, 1253, 1161 cm⁻¹; EIMS m/z 274.

Example 47: Preparation of(E)-3-(4-(trifluoromethoxy)phenyl)but-2-en-1-ol (C320)

Based on procedure of G Rai, A A Sayed, W A Lea, H Luecke, H Chakrapani,S Prasr-Nielsen, A Jadhav, W Leister, M Shen, J Inglese, C P Austin, LKeefer, E S Arner, A Simeonov, D J Maloney, D L Williams and CJ Thomasin J Med Chem (2009) 52(20), 6474-6483. A 1.5 M toluene solution ofdiisobutylaluminum hydride (37.1 mL, 48.1 mmol) was added at a dropwiserate over 90 minutes to another toluene solution of (E)-ethyl3-(4-(trifluoromethoxy)phenyl)but-2-enoate (6.0 g, 21.88 mmol) at −78°C. The addition rate was adjusted to maintain temperature between −71and −78° C. After 4 days at ambient temperature, the reaction mixturewas poured into a dilute hydrochloric acid slush (500 mL) and extractedwith toluene (3×150 mL). The combined organic extracts were washed withwater (300 mL) and brine (200 mL), dried over magnesium sulfate, andconcentrated under reduced pressure. Chromatography on a silica column,eluting with 5:1 hexane/ethyl acetate afforded two fractions. Thedesired product was isolated from Fraction 2 as a pale yellowish liquid(3.0 g, 59%): ¹H NMR (400 MHz, CDCl₃) δ 7.42 (dt, J=8.7, 1.2 Hz, 2H),7.17 (d, J=8.7 Hz, 2H), 5.96 (td, J=6.6, 1.2 Hz, 1H), 4.37 (d, J=6.2 Hz,2H), 2.07 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 148.43, 141.55, 136.56,127.37, 127.11, 124.33, 121.77, 120.73, 119.22, 116.66, 59.91, 16.08;¹⁹F NMR (376 MHz, CDCl₃) δ −57.86; EIMS m/z 232; IR 1253.9 (m), 1209.4(m), 1158.0 (m) cm⁻¹.

Example 48: Preparation of(E)-3-(4-(trifluoromethoxy)phenyl)but-2-en-1-yl)oxy)tetrahydro-2H-pyran(C321)

An ice-cold suspension of(E)-3-(4-(trifluoromethoxy)phenyl)but-2-en-1-ol (C320) (2.9 g, 12.49mmol) in diethyl ether (15 mL) was treated with neat3,4-dihydro-2H-pyran (1.786 g, 21.23 mmol). After stirring for 10minutes, solid p-toluenesulfonic acid (0.119 g, 0.624 mmol) was added.The reaction mixture was allowed to warm slowly to ambient temperatureunder nitrogen over 14 hours. Neat 3,4-dihydro-2H-pyran (0.2 g, 2.38mmol) was added, and the mixture was stirred at ambient temperature foran additional 62 hours. The reaction mixture was washed with diluteaqueous sodium hydroxide (0.2 N, 150 mL), water (100 mL), and brine (70mL), dried over magnesium sulfate, concentrated under reduced pressure,applied to a dry flash silica column and eluted with 10:1 hexane/ethylacetate. The desired fraction was concentrated under reduced pressureand dried in vacuo at 40° C. for 14 hours to leave a pale yellowishliquid (3.4 g, 85%): ¹H NMR (400 MHz, CDCl₃) δ 7.43 (dt, J=8.8, 2.1 Hz,2H), 7.16 (d, J=8.4 Hz, 2H), 5.94 (t, J=6.45 Hz, 1H), 4.69 (t, J=3.4 Hz,1H), 4.44 (dd, J=12.7, 6.6 Hz, 1H), 4.23 (dd, J=13.1, 7.0 Hz, 1H),3.98-3.83 (m, 1H), 3.63-3.43 (m, 1H), 2.07 (s, 3H), 1.86 (dd, J=8.8, 3.5Hz, 1H), 1.80-1.71 (m, 1H), 1.67-1.49 (m, 5H); ¹⁹F NMR (376 MHz, CDCl₃)δ −57.85; ¹³C NMR (101 MHz, CDCl₃) δ 148.31, 141.66, 136.81, 127.09,125.17, 124.32, 121.77, 120.65, 119.22, 116.66, 98.15, 94.69, 64.15,62.98, 30.69, 25.47, 19.54, 16.16; EIMS m/z 316); IR (thin film) 1253,1207, 1051 cm⁻¹.

Example 49: Preparation of(E)-2-((3-(4-nitrophenyl)allyl)oxy)tetrahydro-2H-pyran (C322)

To a solution of (E)-3-(4-nitrophenyl)prop-2-en-1-ol (1.5 g, 8.37 mmol)in diethyl ether (56 mL) was added 3,4-dihydro-2H-pyran (1.298 mL, 14.23mmol) forming a tan slurry. p-Toluenesulfonic acid (0.080 g, 0.419 mmol)was added, and the reaction mixture was stirred for 10 minutes.Tetrahydrofuran (15 mL) was added to improve the solubility, and after30 minutes, the reaction mixture had become clear. The reaction mixturewas allowed to stir at room temperature overnight. The reaction mixturewas quenched with saturated aqueous sodium carbonate, and the layerswere separated. The organic layer was dried over sodium sulfate,filtered, and concentrated to afford the title compound as a yellow oil(2.25 g, 97%): ¹H NMR (400 MHz, CDCl₃) δ 8.26-8.09 (m, 2H), 7.57-7.44(m, 2H), 6.79-6.63 (m, 1H), 6.51 (ddd, J=16.0, 5.8, 5.2 Hz, 1H), 4.71(dd, J=4.2, 3.0 Hz, 1H), 4.46 (ddd, J=13.9, 5.2, 1.7 Hz, 1H), 4.20 (ddd,J=13.9, 5.9, 1.6 Hz, 1H), 3.91 (ddd, J=11.2, 8.2, 3.3 Hz, 1H), 3.65-3.47(m, 1H), 1.96-1.36 (m, 6H); ¹³C NMR (101 MHz, CDCl₃) δ 146.95, 143.36,131.36, 129.36, 126.93, 123.98, 98.33, 67.10, 62.34, 30.58, 25.41,19.44; IR (thin film) 2939, 2849, 1595, 1513, 1339 cm⁻¹.

Example 50: Preparation oftrans-(2,2-dichloro-3-methyl-3-(4-(trifluoromethoxy)phenyl)cyclopropyl)methanol(C323)

p-Toluenesulfonic acid (0.076 g, 0.401 mmol) was added to an ice-coldsolution oftrans-2-((2,2-dichloro-3-methyl-3-(4-(trifluoromethoxy)phenyl)cyclopropyl)methoxy)tetrahydro-2H-pyran(C230) in methanol (40 mL) and allowed to warm to ambient temperatureunder nitrogen over 14 hours. The volatiles were removed under reducedpressure. The residue was dissolved in ethyl acetate (70 mL), washedwith saturated aqueous sodium bicarbonate (50 mL). The solution waswashed with water (50 mL) and brine (50 mL), dried over magnesiumsulfate, concentrated under reduced pressure and dried in vacuo at 44°C. for 6 hours to leave a yellow gum (1.86 g, 74%): ¹H NMR (400 MHz,CDCl₃) δ 7.35 (dt, J=8.9, 2.0 Hz, 2H), 7.23-7.17 (m, 2H), 4.08-4.00 (m,1H), 3.97-3.89 (m, 1H), 2.18 (dd, J=7.7, 7.2 Hz, 2H), 1.71 (t, J=5.6 Hz,1H), 1.54 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −57.84; ¹³C NMR (101 MHz,CDCl₃) δ 148.31, 148.29, 140.97, 130.13, 130.05, 124.28, 121.72, 120.98,120.91, 119.16, 116.61, 59.61, 38.65, 38.27, 19.84; EIMS m/z 283 (M-Cl);IR (thin film) 1254, 1206, 1160 cm⁻¹.

Example 51: Preparation of (E)-3-chloro-5-(4-methoxystyryl) benzaldehyde(C324)

To a stirred solution of 3-bromo-5-chlorobenzaldehyde (20.0 g, 91.32mmol) in dimethylacetamide, 1-methoxy-4-vinylbenzene (18.3 g, 136.9mmol) and triethylamine (50 mL, 273.96 mmol) were added, and thereaction mixture was degassed with argon for 5 minutes. Palladium(II)acetate (410 mg, 1.83 mmol) and tri-o-tolylphosphine (1.11 g, 3.65 mmol)were added, and the resulting reaction mixture was heated to 100° C. for16 hours. The reaction mixture was poured into water and extracted withethyl acetate. The combined organic layer was dried over sodium sulfateand concentrated under reduced pressure. The resulting crude materialwas purified by flash column chromatography using 5-10% ethyl acetate inpetroleum ether as the eluent to afford the title compound as a yellowsolid (13.5 g, 54%): ¹H NMR (300 MHz, CDCl₃) δ 9.99 (s, 1H), 7.85 (s,1H), 7.69 (s, 2H), 7.47 (d, J=8.4 Hz, 2H), 7.16 (d, J=16.2 Hz, 1H), 6.94(t, J=8.4 Hz, 3H), 3.84 (s, 3H); ESIMS m/z 273 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 51:

(E)-2-Chloro-5-(4-methoxystyryl)benzaldehyde (C325)

Isolated as a pale yellow solid (11.8 g, 27%): ¹H NMR (300 MHz, CDCl₃) δ10.45 (s, 1H), 8.02 (s, 1H), 7.62 (d, J=6.4 Hz, 1H), 7.46-7.40 (m, 3H),7.12 (d, J=16.4 Hz, 1H), 6.95-6.90 (m, 3H), 3.95 (s, 3H); ESIMS m/z 273([M+H]⁺).

(E)-3-Fluoro-5-(4-methoxystyryl)benzaldehyde (C326)

Isolated as a pale yellow solid (25 g, 57%): ¹H NMR (300 MHz, CDCl₃) δ10 (s, 1H), 7.77 (s, 1H), 7.48-7.40 (m, 4H), 7.16 (d, J=16.2 Hz, 1H),6.94 (t, J=15.6 Hz, 3H), 3.84 (s, 3H); ESIMS m/z 275 ([M+H]⁺).

(E)-2-Fluoro-5-(4-methoxystyryl)benzaldehyde (C327)

Isolated as an off-white solid (0.25 g, 20%): ¹H NMR (400 MHz, CDCl₃) δ10.43 (s, 1H), 7.90 (d, J=8.4 Hz, 1H), 7.54-7.46 (m, 4H), 7.20 (d,J=16.0 Hz, 1H), 6.94-6.90 (m, 3H), 3.85 (s, 3H); ESIMS m/z 274 ([M+H]⁺).

(E)-2-Chloro-4-(4-methoxystyryl)benzaldehyde (C328)

Isolated as an off-white solid (8.0 g, 57%): ¹H NMR (400 MHz, CDCl₃) δ10.41 (s, 1H), 7.97 (dd, J=2.4, 6.8 Hz, 1H), 7.71-7.67 (m, 1H), 7.44 (d,J=8.0 Hz, 2H), 7.18-7.13 (m, 1H), 7.08-7.04 (m, 1H), 6.95-6.90 (m, 3H),3.85 (s, 3H); ESIMS m/z 257 ([M+H]⁺).

(E)-2-Fluoro-4-(4-methoxystyryl)benzaldehyde (C329)

Isolated as a brown solid (15 g, 78%): ¹H NMR (400 MHz, CDCl₃) δ 10.35(s, 1H), 7.83 (t, J=7.6 Hz, 1H), 7.48 (d, J=8.8 Hz, 2H), 7.35 (d, J=8.4Hz, 1H), 7.23-7.18 (m, 2H), 6.96-6.91 (m, 3H), 3.95 (s, 3H); ¹⁹F NMR(376 MHz, CDCl₃) δ 122.26; ESIMS m/z 257 ([M+H]⁺).

(E)-3-(4-methoxystyryl)benzaldehyde (C330)

Isolated as a brown solid (18 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 10.15(s, 1H), 8.00 (s, 1H), 7.73 (d, J=7.2 Hz, 2H), 7.53-7.46 (m, 3H), 7.17(d, J=16.8 Hz, 1H), 7.01 (d, J=16.0 Hz, 1H), 6.92 (d, J=8.8 Hz, 2H),3.84 (s, 3H); ESIMS m/z 239 ([M+H]⁺).

(E)-4-(4-Methoxystyryl)benzaldehyde (C331)

Isolated as a light brown solid (9.0 g, 47%): ¹H NMR (400 MHz, CDCl₃) δ10 (s, 1H), 7.84 (d, J=8.0 Hz, 2H), 7.61 (d, J=7.6 Hz, 2H), 7.48 (d,J=8.0 Hz, 2H), 7.23 (t, J=7.6 Hz, 1H), 7.00 (d, J=16.0 Hz, 1H), 6.92 (d,J=8.8 Hz, 2H), 3.84 (s, 3H).

Example 52: Preparation of(E)-1-chloro-3-(difluoromethyl)-5-(4-methoxy-styryl)benzene (C332)

To a stirred solution of (E)-3-chloro-5-(4-methoxystyryl) benzaldehyde(C146) (13 g, 47.79 mmol) in dichloromethane (130 mL) was addeddiethylaminosulfur trifluoride (31.5 mL, 238.97 mmol) at −78° C. Theresulting solution was stirred for 20 hours at room temperature. Thereaction mixture was cooled to 0° C., and a solution of saturatedaqueous sodium bicarbonate was added dropwise. The layers were separatedand the aqueous layer was extracted with dichloromethane (3×75 mL). Thecombined organic layer was washed with water and brine, dried oversodium sulfate, and concentrated. The crude material was purified byflash column chromatography using 10-20% ethyl acetate in hexanes as theeluent to afford the title compound as a pale yellow oil (13.1 g, 94%):¹H NMR (400 MHz, CDCl₃) δ 7.55 (s, 1H), 7.45 (d, J=8.8 Hz, 3H), 7.34 (s,1H), 7.10 (d, J=16 Hz, 1H), 6.90 (t, J=8.4 Hz, 3H), 6.61 (t, J=56.4 Hz,1H), 3.80 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −111.72.

The following compounds were prepared in like manner to the procedureoutlined in Example 52:

(E)-1-Chloro-2-(difluoromethyl)-4-(4-methoxystyryl)benzene (C333)

Isolated as an off-white solid (12 g, 94%): ¹H NMR (300 MHz, CDCl₃) δ7.75 (s, 1H), 7.51-7.44 (m, 3H), 7.37 (d, J=8.4 Hz, 1H), 7.13 (d, J=6.6Hz, 1H), 7.06 (s, 1H), 6.95-6.89 (m, 3H), 3.95 (s, 3H); ¹⁹F NMR (282MHz, CDCl₃) δ −115.31; ESIMS m/z 295 ([M+H]⁺).

(E)-1-(Difluoromethyl)-3-fluoro-5-(4-methoxystyryl)benzene (C334)

Isolated as an off-white solid (20 g, 75%); ¹H NMR (300 MHz, CDCl₃) δ7.46 (d, J=8.0 Hz, 2H), 7.38 (s, 1H), 7.28 (s, 1H), 7.08 (t, J=16.2 Hz,2H), 6.92 (t, J=15.6 Hz, 3H), 6.63 (t, J=56.0 Hz, 1H), 3.84 (s, 3H);ESIMS m/z 279 ([M+H]⁺).

(E)-2-(Difluoromethyl)-1-fluoro-4-(4-methoxystyryl)benzene (C335)

Isolated as an off-white solid (14.0 g, 70%): ¹H NMR (300 MHz, CDCl₃) δ7.69 (d, J=9.0 Hz, 1H), 7.57-7.53 (m, 1H), 7.45 (d, J=9.9 Hz, 2H),7.13-7.06 (m, 2H), 7.00-6.89 (m, 4H), 3.85 (s, 3H); ESIMS m/z 279([M+H]⁺).

(E)-2-Chloro-1-(difluoromethyl)-4-(4-methoxystyryl)benzene (C336)

Isolated as an off-white solid (18.0 g, 90%): ¹H NMR (400 MHz, CDCl₃) δ7.61 (d, J=8.0 Hz, 1H), 7.51 (s, 1H), 7.47-7.43 (m, 3H), 7.14-7.07 (m,1H), 6.94-6.80 (m, 4H), 3.85 (s, 3H); ESIMS m/z 294 ([M+H]⁺).

(E)-1-(Difluoromethyl)-2-fluoro-4-(4-methoxystyryl)benzene (C337)

Isolated as a pale yellow solid (9 g, 55%): ¹H NMR (400 MHz, CDCl₃) δ7.54 (t, J=8.0 Hz, 1H), 7.46 (d, J=8.8 Hz, 2H), 7.32 (d, J=8.0 Hz, 1H),7.22 (d, J=11.6 Hz, 1H), 7.11 (d, J=16.4 Hz, 1H), 7.01-6.83 (m, 4H),3.95 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −113.57, −114.25, −120.33;ESIMS m/z 279 ([M+H]⁺).

(E)-1-(Difluoromethyl)-3-(4-methoxystyryl)benzene (C338)

Isolated as a pale yellow solid (6 g, 68%): ¹H NMR (300 MHz, CDCl₃) δ7.62-7.56 (m, 2H), 7.48-7.34 (m, 4H), 7.11 (d, J=16.5 Hz, 1H), 7.00 (s,1H), 6.95-6.89 (t, 2H), 6.66 (t, 1H), 3.95 (s, 3H); ¹⁹F NMR (282 MHz,CDCl₃) δ −110.84; ESIMS m/z 261 ([M+H]⁺).

(E)-1-(Difluoromethyl)-4-(4-methoxystyryl)benzene (C339)

Isolated as an off-white solid (15.4 g, 75%): ¹H NMR (300 MHz, CDCl₃) δ7.57-7.45 (m, 6H), 7.12 (d, J=15.9 Hz, 1H), 7.00-6.89 (m, 3H), 6.64 (t,J=57 Hz, 1H), 3.92 (s, 3H); ESIMS m/z 260.17 ([M+H]⁺).

Example 53: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(C340)

To a solution of2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoicacid (C67) (2 g, 4.41 mmol) and N-ethyl-N-isopropylpropan-2-amine (1.152mL, 6.61 mmol) in tetrahydrofuran (29.4 mL) was added ethylcarbonochloridate (0.464 mL, 4.85 mmol). The reaction mixture wasstirred at room temperature for 4 hours. Ammonia (0.5 M in dioxane,17.64 mL, 8.82 mmol) was added, and the reaction mixture was stirred for15 minutes. The reaction mixture was concentrated by rotary evaporationto give a pink foam. The foam was suspended in dichloromethane (15 mL)and stirred vigorously at 0° C. for 30 minutes to give a suspension. Thesolid was collected by vacuum filtration washing multiple times withdichloromethane to remove the pink color, affording the title compoundas a white solid (1.79 g, 90%): ¹H NMR (400 MHz, DMSO-d₆) δ 10.84 (s,1H), 7.91 (s, 1H), 7.76 (d, J=2.6 Hz, 1H), 7.67 (dd, J=8.8, 2.6 Hz, 1H),7.64-7.60 (m, 2H), 7.55 (d, J=1.8 Hz, 2H), 7.46 (d, J=8.7 Hz, 1H), 3.61(d, J=8.6 Hz, 1H), 3.50 (d, J=8.5 Hz, 1H); ESIMS m/z 453 ([M+H]⁺); IR(thin film) 3183, 1665, 1587, 1610, 1566, 1547, 1417 cm⁻¹.

Example 54: Preparation oftrans-2-chloro-N-(2-cyano-4-nitrophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F229)

A suspension of2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(C340) (600 mg, 1.326 mmol), 2-bromo-5-nitrobenzonitrile (361 mg, 1.591mmol), cesium carbonate (605 mg, 1.856 mmol),tris(dibenzylideneacetone)dipalladium(O) (Pd₂(dba)₃, 36.4 mg, 0.040mmol), and Bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 69.0mg, 0.119 mmol) in 1,4-dioxane (8.9 mL) was evacuated under vacuum andbackfilled with nitrogen three times. The reaction mixture was sealedunder a blanket of nitrogen and heated to 60° C. by microwaveirradiation for 2 hours. The reaction mixture was diluted with ethylacetate and filtered through Celite®. The solvent was removed via rotaryevaporation to give a deep red solid. The solid was suspended indichloromethane (10 mL) and then collected by vacuum filtration, washingwith more dichloromethane to afford the title compound as a red solid(0.598 g, 75%): ¹H NMR (400 MHz, Acetone-d₆) missing one amide NH inbaseline b 10.26 (s, 1H), 8.73 (d, J=2.6 Hz, 1H), 8.62 (dd, J=9.2, 2.6Hz, 1H), 8.55 (d, J=9.2 Hz, 1H), 8.13 (d, J=2.6 Hz, 1H), 7.89 (dd,J=8.8, 2.6 Hz, 1H), 7.55 (d, J=8.8 Hz, 1H), 7.51 (s, 3H), 3.67 (d, J=8.3Hz, 1H), 3.45 (d, J=8.3 Hz, 1H); HRMS-ESI (m/z) [M+H]⁺ calcd forC₂₄H₁₄Cl₅N₄O₄, 596.9452; found, 596.9441; IR (thin film) 3341, 3074,1673, 1568, 1545, 1509, 1473, 1413 cm⁻¹.

The following compounds were prepared in like manner to the procedureoutlined in Example 54:

2-Chloro-N-(2-cyano-5-methylphenyl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F230)

Isolated as a white solid (0.1052 g, 84%).

2-Chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-methyl-2-nitrophenyl)benzamide(F231)

Isolated as a yellow foam (0.0302 g, 31%).

2-Chloro-N-(2-cyano-4-(trifluoromethyl)phenyl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F232)

Isolated as an orange solid (0.0357 g, 35%).

2-Chloro-N-(4-cyano-3-fluorophenyl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F233)

Isolated as a pale yellow solid (0.0461 g, 49%).

2-Chloro-N-(4-cyano-3-methoxyphenyl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F234)

Isolated as a pale yellow solid (0.0151 g, 16%).

2-Chloro-N-(4-cyano-3-(trifluoromethyl)phenyl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F235)

Isolated as a pale yellow solid (0.0644 g, 63%).

2-Chloro-N-(2-cyano-3-fluorophenyl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F298)

Isolated as a white solid (0.0893 g, 71%).

2-Chloro-N-(2-cyano-6-fluorophenyl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F299)

Isolated as a white solid (0.0823 g, 65%).

2-Chloro-N-(2-cyano-6-fluoro-4-methylphenyl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F300)

Isolated as a white solid (0.086 g, 67%).

2-Chloro-N-(4-chloro-2-cyanophenyl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F301)

Isolated as a white solid (0.098 g, 76%).

2-Chloro-N-(3-chloro-2-cyanophenyl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F302)

Isolated as a white solid (0.109 g, 84%).

N-(5-Bromo-2-cyanophenyl)-2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F303)

Isolated as a white solid (0.111 g, 80%).

2-Chloro-N-(2-cyano-3-methylphenyl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F304)

Isolated as a white solid (0.1072 g, 86%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-dicyanophenyl)benzamide(F287)

Isolated as a tan solid (0.043 g, 33%).

Example 55: Preparation oftrans-N-(5-bromo-1,3,4-thiadiazol-2-yl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF133)

To a solution oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzoicacid (C67) (0.100 g, 0.220 mmol) and 5-bromo-1,3,4-thiadiazol-2-amine(0.040 g, 0.220 mmol) in ethyl acetate (2.0 mL) was added pyridine(0.036 mL, 0.441 mmol) followed by2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (T3P®)as a 50% solution in ethyl acetate (0.210 g, 0.331 mmol). The reactionmixture was stirred for 72 hours at room temperature. The reactionmixture was then diluted with ethyl acetate, and Celite® was added tothe mixture. The solvents were removed under reduced pressure to give adry powder which was subsequently purified by flash columnchromatography using 0-35% ethyl acetate/hexanes as eluent to afford thetitle compound as a white solid (0.075 g, 55%).

The following compounds were prepared in like manner to the procedureoutlined in Example 55:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(thiophen-2-yl)thiazol-2-yl)benzamide(PF135)

Isolated as a white solid (0.046 g, 34%).

trans-2-Chloro-N-(5-cyanopyridin-2-yl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF143)

Isolated as a white solid (0.065 g, 53%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-fluoropyrimidin-2-yl)benzamide(F222)

Isolated as a white solid (0.087 g, 72%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(6-fluoropyridin-2-yl)benzamide(F240)

Isolated as a white solid (0.104 g, 78%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F241)

Isolated as a white solid (0.106 g, 85%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-fluoro-3-methylpyridin-2-yl)benzamide(F242)

Isolated as a white solid (0.103 g, 83%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(pyrimidin-2-yl)benzamide(F294)

Isolated as a white solid (0.021 g, 18%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(pyrimidin-5-yl)benzamide(F295)

Isolated as a white solid (0.094 g, 80%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(pyrimidin-4-yl)benzamide(F296)

Isolated as a white solid (0.059 g, 51%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-fluoro-4-methylpyridin-2-yl)benzamide(F297)

Isolated as a white solid (0.105 g, 84%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-fluoropyrimidin-4-yl)benzamide(F318)

Isolated as a white solid (0.030 g, 25%).

trans-N-(4-Amino-3,5-difluoropyridin-2-yl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F345)

Isolated as a white solid (0.104 g, 65%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-nitrophenyl)benzamide(F348)

Isolated as a yellow glass (0.146 g, 67%).

N-(4-Amino-3,5-difluoropyridin-2-yl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F370)

Isolated as a white solid (0.064 g, 50%).

N-(4-Amino-3,5-difluoropyridin-2-yl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F371)

Isolated as a white solid (0.062 g, 49%).

N-(4-Amino-3,5-difluoropyridin-2-yl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F372)

Isolated as a white solid (0.080 g, 63%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(5-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,4-difluorophenyl)carbamate(F519)

Isolated as a white solid (0.159 g, 92%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(5-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,4-difluorophenyl)carbamate(F520)

Isolated as a white solid (0.154 g, 900/).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-4,6-difluorophenyl)carbamate(F521)

Isolated as a white solid (0.112 g, 65%/).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-nitrophenyl)benzamide(F554)

Isolated as a yellow film (0.127 g, 81%/).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-nitrophenyl)benzamide(F555)

Isolated as a yellow film (0.138 g, 88%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-nitrophenyl)benzamide(F556)

Isolated as a yellow film (0.115 g, 75%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-nitrophenyl)benzamide(F557)

Isolated as a yellow film (0.128 g, 81%).

N-(3-Bromo-4,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F583)

Isolated as a white foam (0.188 g, 88%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(5-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,4-difluorophenyl)carbamate(F610)

Isolated as a white solid (0.138 g, 83%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(5-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamido)-2,4-difluorophenyl)carbamate(F611)

Isolated as a white solid (0.164 g, 94%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-4,6-difluorophenyl)carbamate(F612)

Isolated as a white solid (0.090 g, 38%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-4-fluorophenyl)carbamate(F613)

Isolated as a white solid (0.075 g, 46%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3,5-difluorophenyl)carbamate(F614)

Isolated as a white solid (0.065 g, 23%).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3,5-difluorophenyl)carbamate(F615)

Isolated as a white solid (0.032 g, 19%).

N-(6-Amino-5-cyanopyridin-2-yl)-2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F292)

Isolated as a white solid (0.0295 g, 16%).

2-Chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-nitropyridin-2-yl)benzamide(F293)

Isolated as a white solid (0.0753 mg, 70%).

N-(5-Bromo-6-fluoropyridin-2-yl)-2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F357)

Isolated as a white solid (0.228 g, 83%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-nitropyridin-3-yl)benzamide(F358)

Isolated as a white solid (0.158 g, 83%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-nitropyridin-3-yl)benzamide(F359)

Isolated as a white solid (0.166 g, 873%).

2-Chloro-N-(2-chloropyridin-4-yl)-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F368)

Isolated as a white solid (0.137 g, 73%).

2-Chloro-N-(2-chloropyridin-4-yl)-5-(1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F369)

Isolated as a white solid (0.152 g, 813%).

2-Chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoro-4-iodopyridin-2-yl)benzamide(F388)

Isolated as a brown solid (0.253 g, 83%).

N-(5-Bromo-6-fluoropyridin-3-yl)-2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F395)

Isolated as a white solid (0.210 g, 76%).

2-Chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(6-fluoro-5-methylpyridin-3-yl)benzamide(F396)

Isolated as a white foam (0.217 g, 88%).

N-(6-Acetamidopyridin-2-yl)-2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F494)

Isolated as a white solid (0.137 g, 71%).

tert-Butyl(6-(2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)pyridin-2-yl)carbamate(F505)

Isolated as a white solid (0.271 g, 84%).

tert-Butyl(6-(2-chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamido)pyridin-2-yl)carbamate(F506)

Isolated as a white solid (0.229 g, 73%).

tert-Butyl(6-(2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-4-(trifluoromethyl)pyridin-2-yl)carbamate(F507)

Isolated as a white solid (0.266 g, 75%).

tert-Butyl(6-(2-chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamido)-4-(trifluoromethyl)pyridin-2-yl)carbamate(F508)

Isolated as a white solid (0.282 g, 81%).

N-(4-(Benzylamino)-3,5-difluoropyridin-2-yl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F524)

Isolated as a tan solid (0.0423 g, 17%).

2-Chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methoxypyridin-4-yl)benzamide(F544)

Isolated as a white solid (0.022 g, 15%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2-methoxypyridin-4-yl)benzamide(F545)

Isolated as a white solid (0.021 g, 15%).

2-Chloro-N-(3-chloro-2-methoxypyridin-4-yl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F546)

Isolated as a white solid (0.078 g, 54%).

2-Chloro-N-(3-chloro-2-methoxypyridin-4-yl)-5-(trans-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F547)

Isolated as a white foam (0.081 g, 58%).

N-(5-Bromo-2-methoxypyridin-4-yl)-2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F548)

Isolated as a white foam (0.057 g, 37%).

N-(5-Bromo-2-methoxypyridin-4-yl)-2-chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F549)

Isolated as an oil (0.045 g, 30%).

2-Chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(6-methoxypyridin-3-yl)benzamide(F550)

Isolated as a beige solid (0.067 g, 50%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(6-methoxypyridin-3-yl)benzamide(F551)

Isolated as a yellow foam (0.040 g, 31%).

2-Chloro-N-(2-chloro-6-methoxypyridin-3-yl)-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F552)

Isolated as a white solid (0.128 g, 89%).

2-Chloro-N-(2-chloro-6-methoxypyridin-3-yl)-5-(trans-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F553)

Isolated as a beige solid (0.117 g, 84%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-fluoro-5-nitrophenyl)benzamide(F415)

Isolated as a light yellow foam (0.11 g, 83%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-fluoro-5-nitrophenyl)benzamide(F416)

Isolated as a light grey foam (0.114 g, 86%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(3-fluoro-5-nitrophenyl)benzamide(F417)

Isolated as a yellow foam (0.114 g, 87%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3-fluoro-5-nitrophenyl)benzamide(F418)

Isolated as an off-white foam (0.101 g, 75%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1,3-dioxoisoindolin-5-yl)benzamide(F439)

Isolated as a light orange solid (0.260 g, 78%).

trans-tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)carbamate(F468)

Isolated as an off-white solid (0.166 g, 44%).

trans-tert-Butyl-N-((tert-butoxy)carbonyl)-N-(5-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2-fluorophenyl)carbamate(F470)

Isolated as an off-white solid (0.300 g, 77%).

trans-tert-Butyl(5-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2-fluorophenyl)(methyl)carbamate(F471)

Isolated as an off-white solid (0.422 g, 100%).

trans-tert-Butyl(4-(3-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)carbamate(C341 and as known as FC341)

Isolated as an off-white solid (0.205 g, 73%): ¹H NMR (400 MHz, DMSO-d₆)δ 10.81 (s, 1H), 9.82 (s, 1H), 9.31 (s, 1H), 8.18 (s, 1H), 7.88 (dd,J=7.7, 1.9 Hz, 1H), 7.72 (d, J=7.8 Hz, 1H), 7.63 (s, 1H), 7.62-7.45 (m,3H), 7.42-7.36 (m, 1H), 7.27 (dd, J=8.7, 2.4 Hz, 1H), 7.18 (d, J=8.5 Hz,1H), 3.63 (d, J=8.5 Hz, 1H), 3.52 (d, J=8.6 Hz, 1H), 2.18 (s, 3H), 1.48(s, 9H); ESIMS m/z 621 ([M−H]⁻).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-4-fluorophenyl)carbamate(C342 and as Known as FC342)

Isolated as a light brown foam (0.072 g, 37%): ¹H NMR (400 MHz, DMSO-d₆)δ 10.88 (s, 1H), 10.43 (s, 1H), 7.84 (q, J=4.1, 3.2 Hz, 2H), 7.71 (dd,J=8.8, 2.6 Hz, 1H), 7.63 (q, J=1.9 Hz, 1H), 7.57-7.54 (m, 3H), 7.26 (dd,J=8.8, 6.1 Hz, 1H), 7.02 (ddd, J=8.8, 7.8, 3.0 Hz, 1H), 3.61 (dd, J=8.5,2.7 Hz, 1H), 3.51 (d, J=8.5 Hz, 1H), 1.31 (s, 18H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −113.29; ESIMS m/z 759.8 ([M−H]⁻).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2-fluorophenyl)carbamate(C343 and as Known as FC343)

Isolated as an off-white foam (0.056 g, 32%): ¹H NMR (400 MHz, DMSO-d₆)δ 10.91 (s, 1H), 10.49 (s, 1H), 7.91 (d, J=2.6 Hz, 1H), 7.75 (td, J=8.7,4.1 Hz, 2H), 7.63 (t, J=1.9 Hz, 1H), 7.56 (q, J=4.1, 3.4 Hz, 3H), 7.22(t, J=5.2 Hz, 2H), 3.63 (d, J=8.5 Hz, 1H), 3.52 (d, J=8.5 Hz, 1H), 1.40(s, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −131.38; ESIMS m/z 759 ([M−H]⁻).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(4-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,5-difluorophenyl)carbamate(C344 and as Known as FC344)

Isolated as an off-white foam (0.136 g, 86%): ¹H NMR (400 MHz, DMSO-d₆)δ 10.96 (s, 1H), 10.69 (s, 1H), 7.96-7.87 (m, 2H), 7.76 (t, J=5.7 Hz,1H), 7.76 (s, 1H), 7.69 (d, J=8.3 Hz, 1H), 7.61-7.52 (m, 2H), 7.43 (dd,J=8.5, 2.1 Hz, 1H), 3.61 (d, J=8.4 Hz, 1H), 3.47 (d, J=8.5 Hz, 1H), 1.40(s, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −126.31 (d, J=14.3 Hz), −127.07(d, J=14.5 Hz); ESIMS m/z 579 ([M+BOC₂]⁺)

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(4-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,5-difluorophenyl)carbamate(C345 and as Known as FC345)

Isolated as an off-white foam (0.137 g, 86%): Isolated as an off-whitefoam (0.124 g, 78%): ¹H NMR (400 MHz, DMSO-d₆) δ 10.93 (s, 1H), 10.69(s, 1H), 7.97-7.87 (m, 2H), 7.76 (dd, J=8.7, 2.6 Hz, 1H), 7.62 (d, J=1.9Hz, 1H), 7.56 (q, J=3.5, 2.4 Hz, 4H), 3.63 (d, J=8.4 Hz, 1H), 3.52 (d,J=8.5 Hz, 1H), 1.41 (s, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −126.31 (d,J=14.6 Hz), −127.08 (d, J=14.6 Hz); ESIMS m/z 579 ([M+BOC₂]⁺)

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(4-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2,5-difluorophenyl)carbamate(C346 and as Known as FC346)

Isolated as an off-white foam (0.137 g, 86%): ¹H NMR (400 MHz, DMSO-d₆)δ 10.94 (s, 1H), 10.69 (s, 1H), 7.96-7.87 (m, 2H), 7.80 (s, 2H), 7.76(dd, J=8.8, 2.6 Hz, 1H), 7.61-7.52 (m, 2H), 3.63 (d, J=8.5 Hz, 1H), 3.55(d, J=8.5 Hz, 1H), 1.40 (s, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −126.31(d, J=14.5 Hz), −127.08 (d, J=14.7 Hz). ESIMS m/z 615 ([M+BOC₂]⁺)

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(4-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamido)-2,5-difluorophenyl)carbamate(C347 and as Known as FC347)

Isolated as an off-white solid (0.133 g, 82%): ¹H NMR (400 MHz, DMSO-d₆)δ 10.95 (s, 1H), 10.69 (s, 1H), 7.96-7.87 (m, 2H), 7.76 (dd, J=8.8, 2.6Hz, 1H), 7.71 (dd, J=7.1, 1.9 Hz, 1H), 7.61-7.52 (m, 2H), 7.53-7.40 (m,2H), 3.59 (d, J=8.5 Hz, 1H), 3.44 (d, J=8.5 Hz, 1H), 1.40 (s, 18H); ¹⁹FNMR (376 MHz, DMSO-d₆) δ −117.04, −117.28, −117.33, −126.30, −126.34,−127.05, −127.09; ESIMS m/z 563 ([M+BOC₂]⁺).

2-Chloro-5-trans-(2,2-dichloro-3-(3,5-dichlorophenyl)-3-methylcyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F251)

Isolated as a white foam (0.130 g, 71.3%).

2-Chloro-5-trans-(2,2-dichloro-3-(3,5-dichlorophenyl)-3-methylcyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F252)

Isolated as a white solid (0.148 g, 79%).

2-Chloro-5-cis-2,2-dichloro-3-(3,5-dichlorophenyl)-3-methylcyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F253)

Isolated as a white solid (0.061 g, 76%).

Methyl2-(4-(2-chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)-3,3,3-trifluoro-2-hydroxypropanoate(F257)

Isolated as a white foam (0.128 g, 79%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-(3,3,3-trifluoroprop-1-en-2-yl)phenyl)benzamide(F258)

Isolated as a tan solid (0.110 g, 74.4%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-(perfluoropropan-2-yl)phenyl)benzamide(F269)

Isolated as a white solid (0.036 g, 21.8%).

tert-Butyl(4-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)carbamate(F275)

Isolated as a white solid (0.283 g, 77%).

tert-Butyl(4-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)carbamate(F277)

Isolated as a white solid (0.328 g, 89%).

tert-Butyl(4-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)carbamate(F278)

Isolated as a white solid (0.276 g, 79%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F279)

Isolated as a white foam (0.156 g, 85%).

2-Chloro-5-((1S,3S)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F280)

Isolated as a white foam (0.153 g, 84%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F281)

Isolated as a white foam (0.146 g, 77%).

2-Chloro-5-((1S,3S)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F282)

Isolated as a white foam (0.163 g, 86%).

N-(4-Amino-2-methylphenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F283)

Isolated as a tan solid (0.143 g, 60.5%).

N-(4-Amino-2-methylphenyl)-2-chloro-5-((1S,3S)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F284)

Isolated as a white solid (0.161 g, 67.1%).

N-(4-Amino-2-methylphenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F285)

Isolated as a white solid (0.153 g, 52.3%).

N-(4-Amino-2-methylphenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F286)

Isolated as a white solid (0.162 g, 67.6%).

tert-Butyl(4-(2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)carbamate(F290)

Isolated as a white solid (0.193 g, 81%).

N-(4-Amino-2-methylphenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F291)

Isolated as a tan solid (0.104 g, 69%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-fluoro-5-iodopyridin-2-yl)benzamide(F312)

Isolated as a white foam (0.026 g, 17.2%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,4-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F346)

Isolated as a white foam (0.091 g, 57.9%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3-fluoro-4-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F347)

Isolated as a white foam (0.111 g, 77%).

5-(trans)-(3-(4-Bromo-3-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F364)

Isolated as a white foam (0.100 g, 70.1%).

5-(trans)-(3-(3-Bromo-4-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F365)

Isolated as a white foam (0.094 g, 70%).

5-(trans)-(3-(4-Bromo-3-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F366)

Isolated as a white foam (0.101 g, 75%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3-chloro-4-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F367)

Isolated as a white foam (0.092 g, 65%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F374)

Isolated as a white foam (0.094 g, 66.4%).

5-(trans)-(3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F375)

Isolated as a white foam (0.111 g, 78%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F376)

Isolated as a white foam (0.114 g, 79%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-difluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F411)

Isolated as a white foam (0.069 g, 43.9%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F412)

Isolated as a white foam (0.081 g, 55.9%).

5-(trans)-(3-(3-Bromo-5-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F423)

Isolated as a white foam (0.104 g, 72.9%).

5-(trans)-(3-(3-Bromo-5-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2,4-difluorophenyl)benzamide(F424)

Isolated as a white foam (0.108 g, 80%).

N-(1-Benzyl-1H-indol-5-yl)-2-chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F458)

Isolated as a pink solid (0.112 g, 76%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1-methyl-2-oxoindolin-5-yl)benzamide(F459)

Isolated as a white solid (0.075 g, 55.8%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1-methyl-5-(trifluoromethyl)-1H-indazol-3-yl)benzamide(F460)

Isolated as a white solid (0.095 g, 64.9%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(7-fluoro-1H-indol-5-yl)benzamide(F462)

Isolated as a white solid (0.086 g, 65.39%).

2-Chloro-N-(4-chloro-1-methyl-1H-indazol-3-yl)-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-indo-carboxamido)benzamide(F463)

Isolated as a white solid (0.020 g, 14.4%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide(F464)

Isolated as a white solid (0.086 g, 65.6%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-(trifluoromethyl)-1H-indol-5-yl)benzamide(F465)

Isolated as a white solid (0.104 g, 72.7%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-oxoindolin-5-yl)benzamide(F472)

Isolated as a white solid (0.051 g, 38.8%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1-methylindolin-5-yl)benzamide(F473)

Isolated as a yellow foam (0.022 mg, 16.2%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1H-pyrrolo[2,3-c]pyridin-5-yl)benzamide(F474)

Isolated as a tan solid (0.056 g, 42.4%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide(F476)

Isolated as a white solid (0.079 g, 60.2%).

(trans)-N-(3-(3-Amino-6-methyl-1H-indazole-1-carbonyl)-4-chlorophenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide(F477)

Isolated as a white solid (0.016 g, 12.2%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(6-methyl-1H-indazol-3-yl)benzamide(F478)

Isolated as a white solid (0.043 g, 32.8%).

(trans)-N-(3-(5-Aminoisoindoline-2-carbonyl)-4-chlorophenyl)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide(F479)

Isolated as a tan solid (0.048 g, 36.3%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide(F481)

Isolated as a white solid (0.061 g, 47.7%).

Ethyl5-(2-chloro-5-(trans)(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-1H-indole-2-carboxylate(F483)

Isolated as a white solid (0.068 g, 47%).

tert-Butyl5-(2-chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-1H-indole-1-carboxylate(F484)

Isolated as a white solid (0.121 g, 81%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-methyl-1H-indol-5-yl)benzamide(F485)

Isolated as a white foam (0.051 g, 39%).

N-(2-(tert-Butyl)-1H-indol-5-yl)-2-chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F486)

Isolated as a yellow foam (0.087 g, 62%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1-ethyl-1H-indol-5-yl)benzamide(F488)

Isolated as a white foam (0.066 g, 47.7%).

2-chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)benzamide(F490)

Isolated as a white solid (0.098 g, 69%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzamide(F491)

Isolated as an orange foam (0.051 g, 36.8%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1,2,3,4-tetrahydroquinolin-6-yl)benzamide(F492)

Isolated as a yellow foam (0.084 g, 62%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1-(2-fluoroethyl)-1H-indol-5-yl)benzamide(F496)

Isolated as a white solid (0.147 g, 86%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-phenyl-1H-indol-5-yl)benzamide(F497)

Isolated as a white solid (0.091 g, 60.9%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-(4-fluorophenyl)-1,3-dioxoisoindolin-5-yl)benzamide(F504)

Isolated as a white solid (0.056 g, 49.8%).

tert-Butyl5-(2-chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)indoline-1-carboxylate(F509)

Isolated as a white solid (0.283 g, 91%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(indolin-5-yl)benzamide(F511)

Isolated as a brown foam (0.100 g, 77%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-3-oxoisoindolin-5-yl)benzamide(F517)

Isolated as a white solid (0.057 g, 42.4%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-1-oxoisoindolin-5-yl)benzamide(F518)

Isolated as a white solid (0.116 g, 86%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(6-fluoro-1H-indol-5-yl)benzamide(F527)

Isolated as a white solid (0.092 g, 67.7%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1H-indol-4-yl)benzamide(F528)

Isolated as a gold foam (0.080 g, 60.7%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1H-indol-7-yl)benzamide(F529)

Isolated as a tan foam (0.097 g, 73.6%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1-methyl-1H-indol-4-yl)benzamide(F530)

Isolated as a brown foam (0.083 g, 61.5%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(1-methyl-1H-indol-7-yl)benzamide(F531)

Isolated as a tan foam (0.091 g, 67.4%).

2-Chloro-5-(trans)-(2,2-dichloro-3-(3,4-dibromophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F532)

Isolated as a white foam (0.105 g, 79%).

2-Chloro-5-((1R,3R)-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F533)

Isolated as a white foam (0.162 g, 82%).

2-Chloro-5-((1S,3S)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F534)

Isolated as a white foam (0.164 g, 83%).

2-Chloro-N-(2-cyano-4-fluorophenyl)-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F535)

Isolated as a white foam (0.120 g, 30.9%).

2-Chloro-N-(2-cyano-4-fluorophenyl)-5-((1S,3S)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F536)

Isolated as a white foam (0.090 g, 23%).

2-Chloro-5-trans-(2,2-dichloro-3-(3,5-difluoro-4-methoxyphenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F537)

Isolated as a white foam (0.078 g, 76%).

2-Chloro-5-trans-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5,6,7,8-tetrahydroquinolin-6-yl)benzamide(F567)

Isolated as a white foam (0.059 g, 43.5%).

2-Chloro-5-trans-(2,2-dichloro-3-(3,4,5-trifluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F581)

Isolated as a clear colorless oil (0.047 g, 46.3%).

2-Chloro-5-cis-(2,2-dichloro-3-(3,4,5-trifluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F582)

Isolated as a white solid (0.010 g, 9.8%).

trans-N-(2-acetyl-4-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF77)

Isolated as a pale yellow foam (0.358 g, 92%).

trans-N-(4-acetyl-2-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF78)

Isolated as a white solid (0.236 g, 61%).

Example 56: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropane-1-carboxamido)-N-phenylbenzamide(F179)

To a solution oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropane-1-carboxamido)benzoicacid (C243) (0.125 g, 0.259 mmol) in dichloromethane (2.5 mL) were added1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxid hexafluorophosphate (0.108 g, 0.284 mmol) followed bydiisopropylethylamine (0.0840 g, 0.646 mmol), and the resultingpale-yellow solution was stirred for 15 minutes, treated with aniline(0.0290 g, 0.310 mmol), and stirred at room temperature forapproximately 18 hours. The solution was diluted with dichloromethane (5mL), washed with water (5 mL), and the phases were separated and driedby passing them through a phase separator cartridge. The organic phasewas concentrated, purified by flash column chromatography, and driedunder vacuum to provide the title compound as tan solid (0.138 g, 96%).

The following compounds were prepared in like manner to the procedureoutlined in Example 56:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclo-propane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F180)

Isolated as a tan solid (0.037 g, 24%).

trans-N-(4-Acetamidophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropane-1-carboxamido)benzamide(F181)

Isolated as a white solid (0.155 g, 97%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclo-propane-1-carboxamido)-N-(4-(methylamino)phenyl)benzamide(F182)

Isolated as a light green solid (0.139 g, 91%).

trans-2,3-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F216)

Isolated as a white solid (0.059 g, 62%).

trans-2,3-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-phenylbenzamide(F246)

Isolated as a white solid (0.075 g, 77%).

trans-2,3-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F247)

Isolated as an off-white solid (0.014 g, 13%).

trans-N-(4-Acetamidophenyl)-2,3-dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F248)

Isolated as a white solid (0.032 g, 30%).

trans-2,3-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(methylamino)phenyl)benzamide(F249)

Isolated as a yellow-green solid (0.028 g, 27%).

trans-2,4-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F250)

Isolated as an orange solid (0.041 g, 41%).

trans-2,4-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-phenylbenzamide(F254)

Isolated as a white solid (0.012 g, 12%).

trans-N-(4-Acetamidophenyl)-2,4-dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F255)

Isolated as a white solid (0.029 g, 27%).

trans-2,4-dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(methylamino)phenyl)benzamide(F256)

Isolated as a gold-colored solid (0.069 g, 68%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-phenylbenzamide(F259)

Isolated as a tan solid (0.070 g, 71%).

trans-N-(4-Acetamidophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F260)

Isolated as a light-yellow solid (0.038 g, 33%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-(methylamino)phenyl)benzamide(F261)

Isolated as a light-yellow solid (0.054 g, 52%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(PF6)

Isolated as a white solid (0.031 g, 29%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(PF156)

Isolated as a white solid (0.137 g, 92%).

Example 57: Preparation oftrans-N-(2-cyano-4-fluorophenyl)-3-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F267)

To a solution of2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxylic acid(C2) in ethyl acetate (3 mL) were added3-amino-N-(2-cyano-4-fluorophenyl)benzamide (C258) (89 mg, 0.350 mmol)in ethyl acetate (2916 μL) and added pyridine (56.6 μl, 0.700 mmol),followed by 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane2,4,6-trioxide (312 μL, 0.525 mmol) as a 50% solution in ethyl acetate.The solution was stirred for 72 hours at room temperature. The resultingmixture was then concentrated under vacuum. Purification by flash columnchromatography using 0-100% ethyl acetate/hexane as an elutant affordedthe product as an off white foam (0.176 g, 79%).

The following compounds were prepared in like manner to the procedureoutlined in Example 57:

trans-N-(2-Cyano-4-fluorophenyl)-3-(2,2-dichloro-3-(3,4-dichlorophenylcyclopropane-1-carboxamido)benzamide(F268)

Isolated as an off-white foam (0.175 g, 79%).

trans-tert-Butyl(5-(2-chloro-5-((1S,3S)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-2-fluorophenyl)(methyl)carbamate(F471)

Isolated as an off-white solid (0.422 g, quant).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-5-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F558)

Isolated as a colorless oil (0.107 g, 88%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-chloro-3-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F559)

Isolated as a colorless oil (0.098 g, 80%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-(difluoromethyl)-5-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F560)

Isolated as a colorless oil (0.115 g, 97%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-(difluoromethyl)-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F561)

Isolated as a colorless oil (0.115 g, 97%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F562)

Isolated as a colorless oil (0.094 g, 77%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-(difluoromethyl)-3-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F563)

Isolated as a colorless oil (0.087 g, 73%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F564)

Isolated as a colorless oil (0.090 g, 78%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F565)

Isolated as a colorless oil (0.090 g, 78%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-5-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F584)

Isolated as a pale yellow oil (0.055 g, 60%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-chloro-3-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F585)

Isolated as a pale yellow oil (0.046 g, 50%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-(difluoromethyl)-5-fluorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F586)

Isolated as a white foam (0.045 g, 50%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-(difluoromethyl)-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F587)

Isolated as a pale yellow oil (0.045 g, 50%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F588)

Isolated as a white foam (0.055 g, 60%).

2-chloro-5-(trans-2,2-dichloro-3-(4-(difluoromethyl)-3-fluorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F589)

Isolated as a white foam (0.036 g, 40%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F590)

Isolated as a pale yellow oil (0.052 g, 60%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoropyridin-2-yl)benzamide(F591)

Isolated as a white foam (0.043 g, 50%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-5-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F592)

Isolated as a pale yellow oil (0.064 g, 70%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-chloro-3-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F593)

Isolated as a pale yellow oil (0.064 g, 70%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-(difluoromethyl)-5-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F594)

Isolated as a colorless oil (0.053 g, 60%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-(difluoromethyl)-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F595)

Isolated as a colorless oil (0.053 g, 60%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F596)

Isolated as a pale yellow oil (0.064 g, 70%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-(difluoromethyl)-3-fluorophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F597)

Isolated as a pale yellow oil (0.062 g, 70%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F598)

Isolated as a colorless oil (0.043 g, 50%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-(difluoromethyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F599)

Isolated as a white foam (0.051 g, 60%).

2-Chloro-5-(trans)-2,2-dichloro-3-(4-chloro-3-fluorophenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(PF36)

Isolated as a white foam. (0.116 g, 76%).

Example 58: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-(trifluoromethyl)phenyl)benzamide(PF69)

To a solution of2-chloro-N-(4-fluoro-2-(trifluoromethyl)phenyl)-5-nitrobenzamide2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxylic acid(C268) (0.15 g, 0.414 mmol) in methanol (1.3 mL) and water (0.66 mL)were added iron (0.115 g, 2.068 mmol) and ammonium chloride (0.066 g,1.241 mmol). The reaction was heated at 60° C. for 2 hours. The reactionwas filtered through Celite®. The filtrate was concentrated to a slurry,diluted with dichloromethane and washed with water. The organic phasewas dried (magnesium sulfate) and concentrated to give a yellow solid.The solid was then purged with a nitrogen atmosphere, dissolved indichloromethane, charged with triethylamine (0.122 mL, 0.889 mmol), andcooled to 0° C.

To a solution of2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylic acid (C67)(612 mg, 2.041 mmol) in dichloromethane (10 mL) cooled to 0° C. wereadded oxalyl chloride (0.3 mL, 3.43 mmol) followed byN,N-dimethylformamide (0.014 mL, 0.184 mmol). The solution was cappedwith a drying tube and stirred overnight slowly warming to roomtemperature. The resulting acid chloride solution was then concentratedunder vacuum to form a dark brown gum residue. The resultingtrans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarbonyl chlorideresidue was dissolved in dichloromethane resulting in a solution of 1 Nconcentration. A portion of thistrans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarbonyl chloridesolution (0.453 mL, 0.462 mmol) was added to the5-amino-2-chloro-N-(4-fluoro-2-(trifluoromethyl)phenyl)benzamide/triethylaminemixture, and the combined mixture was stirred overnight slowly whilewarming to room temperature. The mixture was then dried to a residue andpurified by flash column chromatography using 0-100% ethylacetate/hexanes as the elutant providing the title compound as anoff-white foam (0.028 g, 9%).

Example 59: Preparation oftrans-N-(4-amino-2-cyanophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F236)

A suspension of2-chloro-N-(2-cyano-4-nitrophenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F229) (618 mg, 1.032 mmol) and 10% palladium on carbon (54.9 mg, 0.052mmol) in ethyl acetate (6.9 mL) was fitted with a balloon filled withhydrogen gas, evacuated under vacuum, and backfilled with hydrogen threetimes. Then, the reaction mixture was stirred under a hydrogenatmosphere overnight. The reaction mixture was filtered through Celite®,rinsing with ethyl acetate, and then the solvent was evaporated to givea yellow foam. The foam was suspended in dichloromethane and then thesolids were collected by vacuum filtration and dried under vacuum. Thecrude material was purified by flash column chromatography using 0-100%ethyl acetate in hexanes as the eluent to afford the title compound as apale yellow powder (0.446 g, 76%).

The following compounds were prepared in like manner to the procedureoutlined in Example 59:

N-(5-Aminopyridin-2-yl)-2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F305)

Isolated as a yellow solid (0.0148 mg, 32%).

N-(5-aminopyridin-3-yl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F362)

Isolated as a white solid (0.0377 g, 37%).

N-(5-Aminopyridin-3-yl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F363)

Isolated as a pale yellow solid (0.0339 g, 31%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(hydroxyamino)pyridin-3-yl)benzamide(F525)

Isolated as a white solid (0.0438 g, 42%).

2-Chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)-N-(5-(hydroxyamino)pyridin-3-yl)benzamide(F526)

Isolated as a yellow solid (0.0523 mg, 46%).

Example 60: Preparation oftrans-N-(2-amino-4-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F361)

To a slurry oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-2-nitrophenyl)benzamide(F348) (0.055 g, 0.093 mmol) in methanol (0.9 mL) and water (0.3 mL)were added iron powder (0.026 g, 0.465 mmol) and ammonium chloride(0.015 g, 0.279 mmol). The slurry was warmed to 55° C. for three hoursthen cooled to room temperature and allowed to stir overnight. Thereaction mixture was filtered thru a plug of Celite®, washing with ethylacetate. The filtrates were concentrated under reduced pressure, and theresidue partitioned between ethyl acetate and water. The phases wereseparated, and the organic layer was washed with brine, poured through aphase separator, and then concentrated. The residue was purified byflash column chromatography using 0-40% ethyl acetate/hexanes as eluentto yield the title compound as a yellow solid (0.033 g, 54%).

The following compounds were prepared in like manner to the procedureoutlined in Example 60:

N-(2-Amino-4-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F575)

Isolated as a yellow solid (0.071 g, 67%).

N-(2-Amino-4-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F576)

Isolated as a yellow solid (0.071 g, 64%).

N-(2-Amino-4-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F577)

Isolated as a yellow solid (0.046 g, 62%).

N-(2-Amino-4-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F578)

Isolated as a yellow solid (0.068 g, 64%).

N-(3-Amino-5-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F431)

Isolated as a light brown foam (0.057 g, 60%).

N-(3-Amino-5-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F432)

Isolated as a light brown foam (0.083 g, 87%).

N-(3-Amino-5-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F433)

Isolated as a light brown foam (0.069 g, 72%).

N-(3-Amino-5-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F419)

Isolated as a brown foam (0.048 g, 47.8%).

Example 61: Preparation of5-(trans-3-(4-aminophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide (F425)

To a slurry of2-chloro-5-(trans-2,2-dichloro-3-(4-nitrophenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F422) (90 mg, 0.172 mmol) in methanol (3 mL) and water (1 mL) wereadded iron powder (48 mg, 0.861 mmol) and ammonium chloride (28 mg,0.517 mmol). The slurry was stirred at 55° C. for 3 hours. The reactionmixture was filtered through a pad of Celite®, washing with ethylacetate, and the filtrate was concentrated. Purification by flash columnchromatography provided the title compound as a yellow foam (0.0707 g,79%).

Example 62: Preparation oftrans-N-(6-aminopyridin-2-yl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F326)

To a solution of tert-butyl(6-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)pyridin-2-yl)carbamate(F505) (216 mg, 0.335 mmol) in dichloromethane (3 mL) was added a 4 Msolution of hydrogen chloride in 1,4-dioxane (0.67 mL, 2.68 mmol). Thereaction mixture was stirred at room temperature overnight, the solventwas evaporated, and the crude residue was partitioned between saturatedaqueous sodium bicarbonate (10 mL) and ethyl acetate (20 mL). The layerswere separated, and the organic layer was dried by passing through aphase separator cartridge. The solvent was then evaporated to afford thetitle compound as a white solid (0.155 g, 85%).

The following compounds were prepared in like manner to the procedureoutlined in Example 62:

N-(6-Aminopyridin-2-yl)-2-chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F327)

Isolated as a white solid (0.140 g, 95%).

N-(6-Amino-4-(trifluoromethyl)pyridin-2-yl)-2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F328)

Isolated as a white solid (0.161 g, 88%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(methylamino)phenyl)benzamidehydrochloride (PF22)

Isolated as a white solid (0.205 g, 97%).

trans-N-(4-Amino-3-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F174)

Isolated as a light brown foam (0.061 g, 91%).

trans-N-(4-amino-2-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F175)

Isolated as a light yellow foam (0.017 g, 85%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-fluoro-4-(methylamino)phenyl)benzamide(F176)

Isolated as a brown solid (0.068 g, 89%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-fluoro-4-(methylamino)phenyl)benzamide(F177)

Isolated as a yellow foam (0.027 g, 76%).

trans-N-(4-Amino-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F195)

Isolated as a white solid (0.053 g, 83%).

trans-2-Chloro-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-(methylamino)phenyl)benzamide(F196)

Isolated as a white solid (0.093 g, 81%).

trans-N-(3-Amino-4-methoxyphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F199)

Isolated as a grey solid (0.083 g, 85%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-methoxy-3-(methylamino)phenyl)benzamide(F200)

Isolated as a grey solid (0.091 g, 92%).

trans-N-(3-Aminophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F201)

Isolated as a white solid (0.063 g, 85%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-(methylamino)phenyl)benzamide(F202)

Isolated as a white solid (0.055 g, 74%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methylamino)phenyl)benzamide(F223)

Isolated as a white solid (0.059 g, 88%).

trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-(methylamino)phenyl)benzamide(F224)

Isolated as a white solid (0.064 g, 92%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-methyl-N-(2-methyl-4-(methylamino)phenyl)benzamide(F225)

Isolated as a white solid (0.078 g, 92%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)-N-methyl-N-(2-methyl-4-(methylamino)phenyl)benzamide(F226)

Isolated as a white solid (0.057 g, 90%).

trans-N-(4-Amino-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F227)

Isolated as a white solid (0.048 g, 92%).

trans-N-(4-Amino-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F228)

Isolated as a white solid (0.043 g, 86%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F313)

Isolated as a white solid (0.115 g, 86%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F314)

Isolated as a white solid (0.115 g, 89%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenylcyclopropane-1-carboxamido)benzamide(F315)

Isolated as a white solid (0.108 g, 84%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F317)

Isolated as a white solid (0.087 g, 84%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide(F341)

Isolated as a white solid (0.104 g, 89%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3-chloro-5-cyanophenyl)cyclopropane-1-carboxamido)benzamide(F344)

Isolated as a white solid (0.073 g, 86%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F353)

Isolated as a light brown solid (0.112 g, 97%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F354)

Isolated as a white solid (0.107 g, 96%).

N-(2-Amino-3,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F360)

Isolated as a white solid (0.031 g, 49%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F402)

Isolated as a grey solid (0.088 g, 87%).

N-(5-Amino-2,4-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F403)

Isolated as a white solid (0.096 g, 84%).

N-(2-Amino-3,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F4043

Isolated as a grey solid (0.021 g, 33%).

N-(2-Amino-5-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F405)

Isolated as a white solid (0.033 g, 61%).

N-(2-Amino-4,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F406)

Isolated as a white solid (0.021 g, 44%).

N-(2-Amino-4,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F408)

Isolated as a white solid (0.013 g, 57%).

trans-N-(3-Amino-4-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F205)

Isolated as an off-white solid (0.078 g, 85%)

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3-methyl-4-(methylamino)phenyl)benzamide(F206)

Isolated as an off-white solid (0.076 g, 88%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-methyl-3-(methylamino)phenyl)benzamide(F207)

Isolated as an off-white solid (0.025 gr, 4478%).

trans-N-(3-Amino-4-fluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F238)

Isolated as an off-white solid (0.153 g, 780%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-fluoro-3-(methylamino)phenyl)benzamide(F239)

Isolated as an off-white foam (0.254 g, 70%).

trans-N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F245)

Isolated as an off-white foam (0.045 g, 58%).

trans-N-(4-Amino-2-methylphenyl)-3-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F264)

Isolated as a yellow roam (0.146 g, 71.4%).

trans-N-(4-Amino-2-methylphenyl)-3-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F265)

Isolated as a yellow foam (0.146 g, 76%).

trans-N-(4-Amino-2-methylphenyl)-3-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F266)

Isolated as a light yellow foam (0.149 g, 78%).

N-(2-Amino-5-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F373)

Isolated as a yellow solid (0.030 g, 73.3%).

N-(2-Amino-3,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F377)

Isolated as a light brown foam (0.040 g, 86%).

N-(4-Amino-3,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F378)

Isolated as a light rose foam (0.087 g, 88%).

N-(4-Amino-3,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F379)

Isolated as a light rose foam (0.057 g, 62.7%).

N-(4-Amino-3,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F380)

Isolated as a light rose foam (0.076 g, 79%).

N-(4-Amino-3,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F381)

Isolated as a light rose foam (0.1 g, 85%).

N-(3-Amino-2-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F426)

Isolated as a light brown foam (0.038 g, 93%).

N-(5-Amino-2-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F427)

Isolated as a light brown foam (0.081 g, 86%).

N-(5-Amino-2-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F428)

Isolated as a light brown foam (0.1 g, 96%).

N-(5-Amino-2-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F429)

Isolated as a light brown foam (0.089 g, 93%).

N-(5-Amino-2-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F430)

Isolated as a light brown foam (0.072 g, 77%).

trans-N-(4-Amino-2,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F568)

Isolated as a light brown foam (0.083 g, 87%).

trans-N-(4-Amino-2,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F569)

Isolated as a light brown foam (0.094 g, 95%).

trans-N-(4-Amino-2,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxamido)benzamide(F570)

Isolated as a light brown foam (0.106 g, 100%).

trans-N-(4-Amino-2,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F571)

Isolated as a light brown foam (0.092 g, 94%).

5-(trans-3-(4-bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2-methyl-4-(methylamino)phenyl)benzamide(F323)

Isolated as a yellow foam (0.0646 g, 97%).

N-(4-Amino-2-methylphenyl)-5-(trans-3-(4-bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide(F324)

Isolated as a yellow solid (0.0449 g, 70%).

N-(3-Amino-2,4-difluorophenyl)-5-(trans-3-(4-bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide(F325)

Isolated as a pale yellow foam (0.0603 g, 63%).

N-(4-Amino-2-methylphenyl)-5-(trans-3-(3-bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide(F336)

Isolate as an orange solid (0.0354 g, 78%).

N-(4-Amino-2-methylphenyl)-5-(trans-3-(3-bromo-5-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide(F337)

Isolated as a tan foam (0.0434 g, 96%).

N-(3-Amino-2,4-difluorophenyl)-5-(trans-3-(3-bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide(F338)

Isolated as an orange foam (0.0435 g, 91%).

N-(3-Amino-2,4-difluorophenyl)-5-(trans-3-(3-bromo-5-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide(F339)

Isolated as a tan foam (0.0499 g, 99%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-vinylphenyl)cyclopropane-1-carboxamido)benzamide(F355)

Isolated as a yellow foam (0.0152 g, 86%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(trans-2,2-dichloro-3-(3-chloro-5-vinylphenyl)cyclopropane-1-carboxamido)benzamide(F356)

Isolated as a yellow foam (0.0345 g, 89%).

N-(3-Amino-2,4-difluorophenyl)-5-((1R,3R)-3-(3-bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide(F579)

Isolated as a yellow foam (0.0751 g, 89%).

N-(5-Amino-2,4-difluorophenyl)-5-((1R,3R)-3-(3-bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide(F580)

Isolated as a yellow foam (0.0385 g, 95%).

N-(3-Amino-2,4-difluorophenyl)-5-(3-trans-(3-bromo-4,5-dichlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide(F621)

Isolated as a white foam (0.045 g, 61%).

N-(3-Amino-2,4-difluorophenyl)-5-(3-trans-(3-bromo-5-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide(F622)

Isolated as a white foam (0.043 g, 58%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-trans-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide(F623)

Isolated as a white foam (0.019 g, 24%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-trans-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxamido)benzamide(F624)

Isolated as a white foam (0.043 g, 53%).

N-(3-Amino-2,4-difluorophenyl)-5-(3-trans-(3-bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chlorobenzamide(F625)

Isolated as a white foam (0.040 g, 43%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-trans-(perfluorophenyl)cyclopropane-1-carboxamido)benzamide(F626)

Isolated as a white foam (0.032 g, 36%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-trans-(3,4,5-trifluorophenyl)cyclopropane-1-carboxamido)benzamide(F627)

Isolated as a white foam (0.016 g, 33%).

N-(3-Amino-2,4-difluorophenyl)-2-chloro-5-(2,2-dichloro-3-cis-(3,4,5-trifluorophenyl)cyclopropane-1-carboxamido)benzamide(F628)

Isolated as a white foam (0.010 g, 39%).

Example 63: Preparation ofN-(2-amino-4,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F407)

To a solution of2-chloro-5-((1R,3R)-2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzoicacid (C240) (0.100 g, 0.220 mmol) andtert-butyl-N-((tert-butoxy)carbonyl)-N-(2-amino-3,5-difluorophenyl)carbamate(C401) (0.076 g, 0.220 mmol) in ethyl acetate (2 mL) was added pyridine(0.036 mL, 0.441 mmol) and2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (T3P®)as a 50% solution in ethyl acetate (0.210 g, 0.331 mmol). The mixturewas warmed to 45° C. for 24 hours. The reaction mixture was cooled toroom temperature and concentrated under a stream of nitrogen. Theresidue was purified by flash column chromatography using 0-30% ethylacetate/hexanes as eluent. Product fractions were combined andconcentrated under reduced pressure. The resulting residue was dissolvedin dichloromethane (2 mL), and a 4 M solution of hydrogen chloride indioxane (0.096 mL, 0.385 mmol) was added. The reaction mixture wasstirred at room temperature for 18 hours. The solvent was evaporatedunder a stream of nitrogen. The residue was partitioned between ethylacetate and saturated aqueous sodium bicarbonate. The phases wereseparated, and the organic layer was washed with saturated aqueoussodium bicarbonate and brine and then passed through a phase separatorto dry. The solvent was evaporated under reduced pressure to afford thetitle compound as a white solid (0.021 g, 17%).

The following compounds were prepared in like manner to the procedureoutlined in Example 63:

N-(2-Amino-4,6-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F409)

Isolated as a white solid (0.025 g, 20%).

N-(2-Amino-3,5-difluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F420)

Isolated as a white solid (0.075 g, 58%).

N-(2-Amino-5-fluorophenyl)-2-chloro-5-((1R,3R)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxamido)benzamide(F421)

Isolated as a light pink solid (0.031 g, 37%).

trans-N-(4-Amino-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F574)

Isolated as a white foam (0.838 g, 99%).

Example 64: Preparation oftrans-N-(4-aminophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamidehydrochloride (PF21)

To a solution oftrans-tert-butyl-(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)phenyl)carbamate (PF13) (0.410 g,0.637 mmol) in dichloromethane (5 mL) was added a 4 M solution ofhydrogen chloride in dioxane (0.478 mL, 1.911 mmol), and the reactionmixture was stirred at room temperature for three hours. The solvent wasevaporated from the reaction under a stream of nitrogen, and theresulting residue was dried under vacuum at room temperature for 72hours to yield the title compound as a white solid (0.371 g, 100%).

Example 65: Preparation oftrans-2-chloro-N-(2-cyano-4-(methylamino)phenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F237)

A suspension ofN-(4-amino-2-cyanophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F236) (60 mg, 0.106 mmol), pyridine (29.7 μL, 0.369 mmol), anddiacetoxycopper (47.9 mg, 0.264 mmol) in dioxane (1.4 mL) was stirred atroom temperature for 15 minutes. Methylboronic acid (15.79 mg, 0.264mmol) was added, and the reaction mixture was heated to 110° C. viamicrowave irradiation for 2 hours. The reaction mixture was filteredthrough Celite®, rinsing with ethyl acetate. The filtrate wasconcentrated, and the crude material was purified by flash columnchromatography using 0-100% ethyl acetate in hexanes as the eluent toafford the title compound as a yellow powder (0.0111 g, 18%).

Example 66: Preparation oftrans-N-(4-(N-acetylacetamido)-2-cyanophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F469)

To a suspension ofN-(4-amino-2-cyanophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F236) (60 mg, 0.106 mmol) in dichloromethane (1.1 mL) were addedtriethylamine (29.4 μL, 0.211 mmol) followed by acetyl chloride (11.29μL, 0.158 mmol). The reaction mixture was sealed under an atmosphere ofnitrogen and stirred overnight at room temperature. Additional acetylchloride (11 μL) and triethylamine (30 μL) were added, and the reactionwas continued for 3 hours. Additional acetyl chloride (11 μL) andtriethylamine (30 μL) were added, and the reaction was continued for 15minutes. The reaction mixture was diluted with dichloromethane andquenched with saturated aqueous ammonium chloride. The organic phase wasdried by passing through a phase separator cartridge, and the solventwas evaporated. The resulting crude residue was purified by flash columnchromatography using 0-100% ethyl acetate in hexanes as the eluent toafford the title compound as a yellow solid (0.0468 g, 68%).

Example 67: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(3,3,3-trifluoropropanamido)phenyl)benzamide(PF25)

To a solution oftrans-N-(4-aminophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamidehydrochloride (PF21) (0.060 g, 0.103 mmol) and triethylamine (0.022 mL,0.155 mmol) in dichloromethane (1 mL) was added 3,3,3-trifluoropropanoylchloride (0.015 g, 0.103 mmol). The reaction mixture was stirred at roomtemperature overnight. The reaction mixture was diluted with ethylacetate and washed with hydrochloric acid (2 N) (2×) and saturatedaqueous sodium bicarbonate (2×). The organic layer was poured through aphase separator and concentrated under reduced pressure to yield thetitle compound as a white solid (0.066 g, 97%).

The following compounds were prepared in like manner to the procedureoutlined in Example 67:

trans-N-(4-Acrylamidophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF26)

Isolated as a white solid (0.034 g, 56%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2-methoxyacetamido)phenyl)benzamide(PF27)

Isolated as a white solid (0.054 g, 84%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2-phenylacetamido)phenyl)benzamide(PF28)

Isolated as a yellow solid (0.055 g, 81%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(3,3,3-trifluoro-N-methylpropanamido)phenyl)benzamide(PF30)

Isolated as a white solid (0.056 g, 83%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2-methoxy-N-methylacetamido)phenyl)benzamide(PF31)

Isolated as a white solid (0.048 g, 83%).

trans-N-(4-Benzamidophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF104)

Isolated as a yellow solid (0.030 g, 36%).

trans-2-Chloro-N-(4-(cyclopropane-1-carboxamido)phenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF107)

Isolated as a white solid (0.037 g, 46%).

trans-2-Chloro-N-(4-(2-cyclopropylacetamido)phenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF163)

Isolated as a white foam (0.050 g, 61%).

Example 68: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2,2-difluorocyclopropane-1-carboxamido)phenyl)benzamide(PF108)

To a solution oftrans-N-(4-aminophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxamido)benzamidehydrochloride (PF21) (0.075 g, 0.129 mmol) in dichloromethane (1.0 mL)was added triethylamine (0.027 mL, 0.194 mmol),1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.037 g,0.194 mmol), 4-dimethylaminopyridine (0.017 g, 0.142 mmol) and2,2-difluorocyclopropanecarboxylic acid (0.016 g, 0.129 mmol). Thereaction mixture was stirred at room temperature overnight and thendirectly loaded onto Celite® and purified by flash column chromatographyusing 0-80% ethyl acetate/hexanes as eluent to afford the title compoundas a white solid (0.054 g, 64%).

The following compounds were prepared in like manner to the procedureoutlined in Example 68:

trans-2-Chloro-N-(4-(1-cyanocyclopropane-1-carboxamido)phenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(PF109)

Isolated as a white foam (0.027 g, 32%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(1-(methoxymethyl)cyclopropane-1-carboxamido)phenyl)benzamide(PF161)

Isolated as a white foam (0.040 g, 47%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(1-(trifluoromethyl)cyclopropane-1-carboxamido)phenyl)benzamide(PF162)

Isolated as a white solid (0.027 g, 31%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(3,3-dimethylbutanamido)phenyl)benzamide(PF164)

Isolated as a white solid (0.064 g, 7%).

Example 69: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2,2,2-trifluoroacetamido)phenyl)benzamide(PF24)

To a solution oftrans-N-(4-aminophenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamidehydrochloride (PF21) (0.060 g, 0.103 mmol) and triethylamine (0.022 mL,0.155 mmol) in dichloromethane (1.0 mL) was added trifluoroaceticanhydride (0.016 mL, 0.114 mmol). The reaction mixture was stirred atroom temperature overnight. The reaction mixture was diluted with ethylacetate and washed with hydrochloric acid (2 N, 2×) and saturatedaqueous sodium bicarbonate (2×). The organic layer was poured through aphase separator and concentrated under reduced pressure to yield thetitle compound (0.051 g, 76%).

The following compounds were prepared in like manner to the procedureoutlined in Example 69:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2,2,2-trifluoro-N-methylacetamido)phenyl)benzamide(PF29)

Isolated as a white foam (0.055 g, 84%).

Example 70: Preparation of trans-methyl(4-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamido)-3-methylphenyl)glycinate(F288)

To a solution oftrans-N-(4-amino-2-methylphenyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F195) (0.070 g, 0.126 mmol) in acetone (1.5 mL) was added potassiumcarbonate (0.035 g, 0.251 mmol) and methyl 2-bromoacetate (0.021 g,0.138 mmol). The reaction mixture was warmed to 50° C. for 16 hours. Thereaction mixture was then concentrated under a stream of nitrogen.Purification by flash column chromatography using 0-50% ethylacetate/hexanes as eluent afforded the title compound as a yellow glass(0.016 g, 20%).

Example 71: Preparation of2-chloro-N-(4-((E)-4-chlorobenzylidene)amino)-2-methylphenyl)-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F510)

4-Chlorobenzaldehyde (12.6 mg, 0.090 mmol) was added in one portion to astirred solution ofN-(4-amino-2-methylphenyl)-2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F284) (50 mg, 0.090 mmol) and anhydrous magnesium sulfate (108 mg,0.900 mmol) in tetrahydrofuran (3 mL) at room temperature. After 12hours, the reaction mixture was concentrated under vacuum on a rotaryevaporator. Purification by silica gel flash chromatography with amobile phase of ethyl acetate and hexanes provided 2-chloro-the titlecompound as a white solid (0.027 g, 42.1%).

Example 72: Preparation oftrans-2-chloro-N-(4-(N-cyano-S-methylsulfinimidoyl)phenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F495)

To a solution oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(methylthio)phenyl)benzamide(F149) (0.180 g, 0.31 mmol) in methanol (3.1 mL) were sequentially addedcyanamide (0.017 g, 0.41 mmol), solid potassium tert-butoxide (0.042 g,0.38 mmol), and N-bromosuccinimide (0.084 g, 0.47 mmol). The reactionmixture was stirred at room temperature for 1 hour. Water was added, andthe mixture was extracted with dichloromethane. The combined organicphases were dried over magnesium sulfate, filtered, and concentrated.The residue was slurried in hexane and vacuum filtered to provide thetitle compound as an off-white foam (0.175 g, 91%).

Example 73: Preparation of2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-2-methylphenyl)benzamide(F480)

Maleic anhydride (16.1 mg, 0.164 mmol) was added in one portion to astirred solution ofN-(4-amino-2-methylphenyl)-2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F284) (83 mg, 0.149 mmol) in anhydrous chloroform (3 mL) at roomtemperature. The mixture was stirred at room temperature for 12 hours.The resulting suspension of white solid was concentrated to drynessunder a stream of nitrogen. The residue was dissolved in aceticanhydride (0.6 mL, 5.95 mmol) and treated with sodium acetate (12.2 mg,0.149 mmol). The reaction mixture was heated at 85° C. for 2 hours, thencooled and stirred at room temperature for 13 hours. The reactionmixture was concentrated under vacuum on a rotary evaporator.Purification by flash chromatography with a mobile phase of ethylacetate and hexanes gave2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-2-methylphenyl)benzamide(0.046 g, 46%) as a yellow solid.

Example 74: Preparation of2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-(methylsulfonamido)phenyl)benzamide(F487)

Methane sulfonyl chloride (32.9 mg, 0.287 mmol) was added in one portionto a stirred solution ofN-(4-amino-2-methylphenyl)-2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F284) (160 mg, 0.287 mmol) and triethyl amine (58.1 mg, 0.574 mmol) indichloromethane (5 mL) at room temperature. After 12 hours, the reactionmixture was concentrated under vacuum on a rotary evaporator.Purification by silica gel flash chromatography with a mobile phase ofethyl acetate and hexanes gave2-chloro-5-(trans)-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(2-methyl-4-(methylsulfonamido)phenyl)benzamide(0.014 g, 7.5%) as a white solid.

Example 75: Preparation oftrans-2-chloro-N-(4-(N-cyano-S-methylsulfonimidoyl)phenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F502)

To a solution oftrans-2-chloro-N-(4-(N-cyano-S-methylsulfinimidoyl)phenyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)benzamide(F495) (0.090 g, 0.15 mmol) in 2:1:1 ethanol:dichloromethane:water (2.0mL) was added potassium carbonate (0.045 g, 0.32 mmol) andmeta-chloroperoxybenzoic acid (0.036 g, 0.16 mmol). The reaction mixturewas stirred at room temperature for 24 hours. Water was added, and themixture was extracted with dichloromethane. The combined organic phaseswere dried over magnesium sulfate, filtered, and concentrated.Purification by reverse phase column chromatography using a 5%acetonitrile to 100% acetonitrile gradient provided the title compoundas a pale yellow powder (0.027 g, 29%).

Example 76: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoro-4-vinylpyridin-2-yl)benzamide(F393)

A solution of2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoro-4-iodopyridin-2-yl)benzamide(F388) (100 mg, 0.145 mmol), bis(triphenylphosphine)palladium(II)dichloride (20.30 mg, 0.029 mmol), and tributyl(vinyl)stannane (0.127mL, 0.434 mmol), in 1,4-dioxane (1 mL) was sealed under an atmosphere ofnitrogen and heated to 90° C. via microwave irradiation for 1 hour. Thereaction mixture was diluted with ethyl acetate, then filtered through10:1 silica gel:potassium carbonate (15 g), rinsing with ethyl acetate.The solution was concentrated, and the resulting crude material wasloaded onto a preload cartridge containing 5:1 silica gel:potassiumfluoride (5 g). Purification by flash column chromatography using 0-50%ethyl acetate in hexanes as the eluent afforded the title compound as atan solid (0.0596 g, 70%).

The following compounds were prepared in like manner to the procedureoutlined in Example 76:

2-Chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(3,5-difluoro-4-(1-fluorovinyl)pyridin-2-yl)benzamide(F394)

Isolated as a tan solid (0.0615 g, 70%).

2-Chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(6-fluoro-5-vinylpyridin-2-yl)benzamide(F397)

Isolated as a tan solid (0.0508 g, 66%).

2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(6-fluoro-5-(1-fluorovinyl)pyridin-2-yl)benzamide(F398)

Isolated as a tan solid (0.0701 g, 88%).

2-Chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(6-fluoro-5-vinylpyridin-3-yl)benzamide(F399)

Isolated as a yellow solid (0.0515 g, 71%).

2-Chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(6-fluoro-5-(1-fluorovinyl)pyridin-3-yl)benzamide(F400)

Isolated as a yellow solid (0.0551 g, 74%).

Example 77: Preparation of2-chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-vinylphenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F289)

A solution of5-(trans-3-(4-bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(4-fluorophenyl)benzamide(F270) (0.065 g, 0.110 mmol), bis(triphenylphosphine)palladium(II)dichloride (0.008 g, 0.011 mmol), and tributyl(vinyl)stannane (0.096 mL,0.105 mmol), in 1,4-dioxane (1 mL) was sealed under an atmosphere ofnitrogen and heated to 90° C. via microwave irradiation for 1 hour. Thereaction mixture was diluted with ethyl acetate, then filtered through10:1 silica gel:potassium carbonate (15 g), rinsing with ethyl acetate.The solution was concentrated, and the resulting crude material wasloaded onto a preload cartridge containing 5:1 silica gel:potassiumfluoride (5 g). Purification by flash column chromatography using 0-25%ethyl acetate in hexanes as the eluent afforded the title compound as apale yellow solid (0.0265 g, 43%).

The following compounds were prepared in like manner to the procedureoutlined in Example 77:

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-vinylphenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F319)

Isolated as a colorless film (0.007 g, 14%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-vinylphenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)-N-methylbenzamide(F329)

Isolated as a pale yellow powder (0.0764 g, 71%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-chloro-3-vinylphenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F349)

Isolated as a yellow foam (0.0366 g, 59%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-5-vinylphenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F350)

Isolated as a yellow foam (0.0909 g, 64%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-chloro-3-vinylphenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F351)

Isolated as a yellow foam (0.0351 g, 73%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-5-vinylphenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F352)

Isolated as a yellow foam (0.0488 g, 78%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-(1-fluorovinyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F382)

Isolated as a yellow foam (0.0684 g, 69%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-(1-fluorovinyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F383)

Isolated as a brown foam (0.0788 g, 96%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-chloro-3-(1-fluorovinyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F384)

Isolated as a yellow foam (0.0657 g, 83%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-chloro-3-(1-fluorovinyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F385)

Isolated as a yellow foam (0.0614 g, 77%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-5-(1-fluorovinyl)phenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F386)

Isolated as a yellow foam (0.0651 g, 82%).

2-Chloro-N-(2-cyano-4-fluorophenyl)-5-(trans-2,2-dichloro-3-(3-chloro-5-(1-fluorovinyl)phenyl)cyclopropane-1-carboxamido)benzamide(F387)

Isolated as a yellow foam (0.0603 g, 76%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-fluoro-4-vinylphenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F389)

Isolated as a yellow foam (0.0357 g, 63%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-fluoro-3-vinylphenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F390)

Isolated as a yellow foam (0.0498 g, 69%).

2-Chloro-5-(trans-2,2-dichloro-3-(3-(trifluoromethyl)-4-vinylphenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F391)

Isolated as a yellow foam (0.0475 g, 66%).

2-Chloro-5-(trans-2,2-dichloro-3-(4-(trifluoromethyl)-3-vinylphenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F392)

Isolated as a yellow foam (0.0307 g, 52%).

tert-Butyl-N-((tert-butoxyl)carbonyl)-N-(3-(2-chloro-5-(2,2-dichloro-3-(4-chloro-3-vinylphenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)carbamate(F522)

Isolated as a yellow foam (0.0276 g, 27%).

tert-Butyl-N-((tert-butoxyl)carbonyl)-N-(3-(2-chloro-5-(2,2-dichloro-3-(3-chloro-5-vinylphenyl)cyclopropane-1-carboxamido)benzamido)-2,6-difluorophenyl)carbamate(F523)

Isolated as a yellow foam (0.0748 g, 76%).

2-Chloro-5-(trans-2,2-dichloro-3-(3,5-difluoro-4-vinylphenyl)cyclopropane-1-carboxamido)-N-(2,4-difluorophenyl)benzamide(F566)

Isolated as a yellow oil (0.0088 g, 10%).

Example 78: Preparation of2-chloro-N-(2-cyano-4-fluorophenyl)-5-(trans-2,2-dichloro-3-(3-chloro-4-((trimethylsilyl)ethynyl)phenyl)cyclopropane-1-carboxamido)benzamide(C348)

A solution of5-(trans-3-(4-bromo-3-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(2-cyano-4-fluorophenyl)benzamide(F320) (0.070 g, 0.114 mmol), bis(triphenylphosphine)palladium(II)dichloride (0.016 g, 0.023 mmol), andtrimethyl((tributylstannyl)ethynyl)silane (0.132 g, 0.341 mmol), in1,4-dioxane (1 mL) was sealed under an atmosphere of nitrogen and heatedto 90° C. via microwave irradiation for 1 hour. The reaction mixture wasdiluted with ethyl acetate, then filtered through 10:1 silicagel:potassium carbonate (15 g), rinsing with ethyl acetate. The solutionwas concentrated, and the resulting crude material was loaded onto apreload cartridge containing 5:1 silica gel:potassium fluoride (5 g).Purification by flash column chromatography using 0-25% ethyl acetate inhexanes as the eluent afforded the title compound as a yellow foam(0.0402 g, 53%): ¹H NMR (400 MHz, Acetone-d₆) δ 10.23 (s, 1H), 9.77 (s,1H), 8.02 (t, J=3.8 Hz, 2H), 7.90 (dd, J=8.8, 2.6 Hz, 1H), 7.71 (dd,J=8.2, 2.9 Hz, 1H), 7.64-7.56 (m, 3H), 7.52 (d, J=8.7 Hz, 1H), 7.42(ddd, J=8.1, 1.8, 0.7 Hz, 1H), 3.65 (d, J=8.3 Hz, 1H), 3.41 (d, J=8.4Hz, 1H), 0.26 (s, 9H); ¹⁹F NMR (376 MHz, Acetone-d₆) δ −116.21; IR (thinfilm) 1667, 1588, 1526, 1494, 1474, 1414 cm⁻¹; HRMS-ESI (m/z) [M+H]⁺calcd for C₂₉H₂₃Cl₄FN₃O₂Si, 632.0292; found, 632.0283.

The following compounds were prepared in like manner to the procedureoutlined in Example 78:

trans-2-chloro-5-(2,2-dichloro-3-(4-chloro-3-((trimethylsilyl)ethynyl)phenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(C349)

Isolated as a brown foam (0.1243 g, 76%); ¹H NMR (400 MHz, Acetone-d₆) δ10.15 (s, 1H), 9.64 (s, 1H), 7.99 (d, J=2.6 Hz, 1H), 7.85 (ddd, J=9.1,4.9, 1.5 Hz, 2H), 7.80 (dd, J=8.8, 2.6 Hz, 1H), 7.60-7.57 (m, 1H), 7.55(d, J=8.3 Hz, 1H), 7.51-7.45 (m, 2H), 7.20-7.12 (m, 2H), 3.64-3.58 (m,1H), 3.36 (d, J=8.3 Hz, 1H), 0.26 (s, 9H); ¹⁹F NMR (376 MHz, Acetone-d₆)δ −120.05; IR (thin film) 1655, 1588, 1543, 1509, 1473 cm⁻¹; HRMS-ESI(m/z) [M+H]⁺ calcd for C₂₈H₂₄C₁₄FN₂O₂Si, 607.034; found, 607.0337.

Example 79: Preparation of2-chloro-N-(2-cyano-4-fluorophenyl)-5-(trans-2,2-dichloro-3-(3-chloro-4-ethynylphenyl)cyclopropane-1-carboxamido)benzamide(F401)

To a stirred solution of2-chloro-N-(2-cyano-4-fluorophenyl)-5-(trans-2,2-dichloro-3-(3-chloro-4-((trimethylsilyl)ethynyl)phenyl)cyclopropane-1-carboxamido)benzamide(C348) (40 mg, 0.063 mmol) in dichloromethane (0.63 mL) and methanol(0.2 mL) was added potassium fluoride (33 mg, 0.567 mmol). The reactionmixture was stirred at room temperature for 3 days. The reaction mixturewas directly loaded onto a prepacked Celite® cartridge. Purification byflash column chromatography provided the title compound as a white foam(0.021 g, 56%).

The following compounds were prepared in like manner to the procedureoutlined in Example 79:

2-Chloro-5-(trans-2,2-dichloro-3-(4-chloro-3-ethynylphenyl)cyclopropane-1-carboxamido)-N-(4-fluorophenyl)benzamide(F410)

Isolated as an orange foam (0.063 g, 85%).

Example 80: Preparation oftrans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-((2,2,2-trifluoroethyl)sulfonyl)phenyl)benzamide(PF17) andtrans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-((2,2,2-trifluoroethyl)sulfinyl)phenyl)benzamide(PF18)

To a solution oftrans-2-chloro-5-((2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-((2,2,2-trifluoroethyl)thio)phenyl)benzamide(PF10) (0.224 g, 0.349 mmol) in dichloromethane (10 mL) was addedmeta-chloroperoxybenzoic acid (0.117 g, 0.523 mmol). The reactionmixture was stirred at room temperature for two hours and then dilutedwith ethyl acetate. The mixture was washed twice with saturated aqueoussodium bicarbonate solution. The organic layer was poured through aphase separator and Celite® was added. The mixture was concentratedunder reduced pressure to give a dry powder. Purification of the powderby flash column chromatography using 0-60% ethyl acetate/hexanes aseluent afforded the title compounds: PF17 isolated as a white solid(0.137 g, 58%); PF18 isolated as a white solid (0.068 g, 30%).

The following compounds were prepared in like manner to the procedureoutlined in Example 80:

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-((trifluoromethyl)sulfonyl)phenyl)benzamide(PF19)

Isolated as a white solid (0.084 g, 39%).

trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N-(4-((trifluoromethyl)sulfinyl)phenyl)benzamide(PF20)

Isolated as a white solid (0.077 g, 37%).

Example 81: Preparation of2-chloro-N-(3,5-difluoropyridin-2-yl)-5-nitrobenzamide (C350)

To a solution of 2-chloro-5-nitrobenzoic acid (2.00 g, 9.92 mmol) and3,5-difluoropyridin-2-amine (1.29 g, 9.92 mmol) in ethyl acetate (50 mL)were added sequentially pyridine (1.6 mL, 19.9 mmol) and2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (T3P®)as a 50% solution in ethyl acetate (9.47 g, 14.88 mmol). The reactionmixture was stirred at room temperature for 16 hours. The reactionmixture was the washed with aqueous hydrochloric acid (1 N), saturatedaqueous sodium bicarbonate, and brine. The organic layer was dried overmagnesium sulfate, filtered and concentrated. The residue was dissolvedin ethyl acetate, and Celite® was added to the solution. The solvent wasremoved under vacuum. Purification by flash column chromatography using0-30% ethyl acetate/hexanes as eluent afforded the title compound as awhite solid (1.97 g, 63%): ¹H NMR (400 MHz, DMSO-d₆) δ 11.20 (s, 1H),8.51-8.28 (m, 3H), 8.12 (ddd, J=10.7, 8.6, 2.6 Hz, 1H), 7.90 (d, J=8.7Hz, 1H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −117.71, −126.11; ESIMS m/z 314([M+H]⁺).

Example 82: Preparation of N-(4-fluorophenyl)-5-nitro-2-vinylbenzamide(C351)

To a suspension of 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane(0.300 mL, 1.769 mmol) in toluene (3.93 mL) were added2-bromo-N-(4-fluorophenyl)-5-nitrobenzamide (C152) (0.200 g, 0.590 mmol)followed by ethanol (2 mL) and 2 M potassium carbonate (0.590 mL, 1.180mmol). The solution was degassed by applying vacuum and then purgingwith nitrogen (3 times). To the reaction mixture was addedtetrakis(triphenylphosphine)palladium(O) (0.034 g, 0.029 mmol), and thereaction mixture was heated at 110° C. under nitrogen for 18 hours.Water (5 mL) was added, and the mixture was extracted with ethylacetate. The organic phase was dried over magnesium sulfate, andconcentrated. Purification by chromatography (0-100% ethylacetate/hexanes) gave N-(4-fluorophenyl)-5-nitro-2-vinylbenzamide (0.060g, 33.8% yield) as a yellow solid: mp 158-160° C., ¹H NMR (400 MHz,CDCl₃) δ 8.40 (d, J=2.3 Hz, 1H), 8.26 (dd, J=8.6, 2.3 Hz, 1H), 7.77 (d,J=8.7 Hz, 1H), 7.69 (s, 1H), 7.64-7.53 (m, 2H), 7.19-7.02 (m, 3H), 5.94(d, J=17.4 Hz, 1H), 5.62 (d, J=11.1 Hz, 1H); ESIMS m/z 287 [(M+H)⁺].

Example 83: Preparation of tert-butyl(4-(5-amino-2-chloro-N-methylbenzamido)-3-methylphenyl)(methyl)carbamate(C352)

To a solution of tert-butyl(4-(2-chloro-N-methyl-5-nitrobenzamido)-3-methylphenyl)(methyl)carbamate(C297) (0.207 g, 0.477 mmol) in ethyl acetate (10 mL) was added 5%palladium on carbon (0.051 g, 0.024 mmol). The suspension was placedunder an atmosphere of hydrogen (balloon) and stirred vigorously for 16hours at room temperature. The suspension was filtered through a pad ofCelite® and washed with ethyl acetate. The filtrate was concentrated,and the residue dried under a stream of nitrogen to afford the titlecompound as a yellow oil (0.200 g, 93%): ¹H NMR (300 MHz, DMSO-d₆) δrotamers 7.28-7.09 (m, 3H), 6.96 (dd, J=8.4, 2.7 Hz, 0.5H), 6.85 (d,J=8.5 Hz, 0.5H), 6.67-6.60 (m, 1H), 6.42-6.28 (m, 1H), 5.50 (s, 1H),5.21 (s, 1H), 3.20 (d, J=2.8 Hz, 3H), 3.09 (s, 1.5H), 3.03 (s, 1.5H),2.25 (d, J=6.3 Hz, 3H), 1.42 (s, 4H), 1.32 (s, 5H); IR (thin film) 3351,2927, 1689, 1641, 1602 cm⁻¹; HRMS-ESI (m/z) [M+H]⁺ calcd forC₂₁H₂₆ClN₃O₃, 404.1735; found, 404.1737.

The following compounds were prepared in like manner to the procedureoutlined in Example 83:

N-(4-Acetamido-2-fluorophenyl)-5-amino-2-chlorobenzamide (C353)

Isolated as a white solid (0.654 g, 93%): ¹H NMR (400 MHz, DMSO-d₆) δ10.14 (s, 1H), 10.01 (s, 1H), 7.67 (dd, J=13.0, 2.3 Hz, 1H), 7.55 (t,J=8.7 Hz, 1H), 7.28-7.21 (m, 1H), 7.11 (d, J=8.6 Hz, 1H), 6.71 (d, J=2.7Hz, 1H), 6.63 (dd, J=8.6, 2.8 Hz, 1H), 5.46 (s, 2H), 2.05 (s, 3H); ¹⁹FNMR (376 MHz, DMSO) 5-120.31; ESIMS m/z 322 ([M+H]⁺).

5-Amino-2-chloro-N-(4-fluoro-2-methylphenyl)-N-methylbenzamide (C354)

Isolated as a white solid (0.230 g, 46%): ¹H NMR (400 MHz, DMSO-d₆)rotamers δ 7.27-6.82 (m, 4H), 6.67-6.57 (m, 1H), 6.35 (dt, J=7.2, 2.7Hz, 1H), 5.49 (s, 1H), 5.22 (s, 1H), 3.19 (s, 2H), 3.03 (s, 1H), 2.28(s, 2H), 2.26 (s, 1H); ¹⁹F NMR (376 MHz, DMSO-d₆) rotamers δ −114.39,−115.17; ESIMS m/z 293 ([M+H]⁺).

N-(4-Acetamido-2-methylphenyl)-5-amino-2-chlorobenzamide (C355)

Isolated as a white solid (0.125 g, 40%): ¹H NMR (400 MHz, DMSO-d₆) δ9.88 (s, 1H), 9.71 (s, 1H), 7.46 (d, J=2.3 Hz, 1H), 7.38 (dd, J=8.5, 2.5Hz, 1H), 7.23 (d, J=8.5 Hz, 1H), 7.11 (d, J=8.6 Hz, 1H), 6.73 (d, J=2.7Hz, 1H), 6.62 (dd, J=8.6, 2.7 Hz, 1H), 5.45 (s, 2H), 2.23 (s, 3H), 2.03(s, 3H); IR (thin film) 3245, 2358, 1652, 1506 cm⁻¹; ESIMS m/z 318([M+H]⁺).

tert-Butyl(4-(5-amino-2-chlorobenzamido)-3-methylphenyl)(methyl)carbamate (C356)

Isolated as a brown foam (1.60 g, 86%): ¹H NMR (400 MHz, DMSO-d₆) δ 9.80(s, 1H), 7.31 (d, J=8.5 Hz, 1H), 7.18-7.07 (m, 3H), 6.75 (d, J=2.7 Hz,1H), 6.64 (dd, J=8.6, 2.7 Hz, 1H), 5.52 (s, 2H), 3.17 (s, 3H), 2.26 (s,3H), 1.40 (s, 9H); ¹³C NMR (101 MHz, DMSO-d₆) δ 165.71, 153.74, 147.60,140.98, 137.16, 133.26, 133.03, 129.80, 127.01, 125.90, 122.96, 115.86,115.30, 113.65, 79.47, 37.08, 27.97, 17.95; ESIMS m/z 388 ([M−H]⁻).

tert-Butyl (4-(5-amino-2-chlorobenzamido)-3-methylphenyl)carbamate(C357)

Isolated as a brown foam (2.09 g, 92%): ¹H NMR (400 MHz, DMSO-d₆) δ 9.68(s, 1H), 9.28 (s, 1H), 7.35 (d, J=2.2 Hz, 1H), 7.26 (dd, J=8.6, 2.4 Hz,1H), 7.18 (d, J=8.6 Hz, 1H), 7.12 (d, J=8.6 Hz, 1H), 6.75 (d, J=2.7 Hz,1H), 6.64 (dd, J=8.6, 2.7 Hz, 1H), 5.64 (s, 2H), 2.21 (s, 3H), 1.48 (s,9H); ¹³C NMR (101 MHz, DMSO-d₆) δ 165.69, 152.77, 147.30, 137.32,137.27, 133.57, 130.14, 129.79, 126.41, 119.77, 115.93, 115.55, 113.84,78.91, 54.86, 28.13, 18.21; ESIMS m/z 374 ([M−H]⁻).

5-Amino-2-chloro-N-(3,5-difluoropyridin-2-yl)benzamide (C358)

Isolated as a white solid (1.78 g, 85%): ¹H NMR (400 MHz, DMSO-d₆) δ10.71 (s, 1H), 8.38 (d, J=2.5 Hz, 1H), 8.06 (ddd, J=9.6, 8.5, 2.6 Hz,1H), 7.12 (d, J=8.6 Hz, 1H), 6.74 (d, J=2.7 Hz, 1H), 6.65 (dd, J=8.6,2.7 Hz, 1H), 5.49 (s, 2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −118.04, −126.68(d, J=6.2 Hz); ESIMS m/z 284 ([M+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-(5-amino-2-chlorobenzamido)-2,6-difluorophenyl)carbamate(C359)

Isolated as a white solid (2.89 g, 59%): ¹H NMR (400 MHz, DMSO-d₆) δ10.28 (s, 1H), 7.67 (td, J=8.8, 5.8 Hz, 1H), 7.24 (td, J=9.3, 1.7 Hz,1H), 7.13 (d, J=8.6 Hz, 1H), 6.73 (d, J=2.7 Hz, 1H), 6.65 (dd, J=8.6,2.8 Hz, 1H), 5.48 (s, 2H), 1.40 (s, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ−123.86, −126.24; ESIMS m/z 496 ([M−H]⁻).

Example 84: Preparation of4-chloro-3-((4-fluorophenyl)carbamoyl)-N-methylbenzenaminium chloride(C360)

To a solution of tert-butyl(4-chloro-3-((4-fluorophenyl)carbamoyl)phenyl) (methyl)carbamate (C276)(0.360 g, 0.950 mmol) in dichloromethane (5 mL) was added a 4 M solutionof hydrogen chloride in dioxane (1.18 mL, 4.75 mmol), and the reactionmixture was stirred at room temperature overnight. The reaction mixturewas concentrated under reduced pressure to afford the title compound asa white solid (0.314 g, 100%): ¹H NMR (400 MHz, DMSO-d₆) δ 10.50 (s,1H), 7.79-7.70 (m, 2H), 7.31 (d, J=8.6 Hz, 1H), 7.23-7.13 (m, 2H),6.91-6.82 (m, 2H), 3.17 (s, 1H), 2.74 (s, 3H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −118.78; ESIMS m/z 279 ([M+H]⁺).

Example 85: Preparation oftert-butyl-N-((tert-butoxyl)carbonyl)-N-(5-(5-amino-2-chlorobenzamido)-2,4-difluorophenyl)carbamate(C361)

To a vial containingtert-butyl-N-((tert-butoxy)carbonyl)-N-(5-amino-2,4-difluorophenyl)carbamate(C398) (0.4 g, 1.16 mmol) were added 2-chloro-5-nitrobenzoic acid (0.23g, 1.16 mmol), 4-dimethylaminopyridine (0.15 g, 1.28 mmol),1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.33 g, 1.74 mmol), anddichloromethane (6 mL). The reaction mixture was stirred at roomtemperature for 18 h then was directly loaded onto a prepacked Celite®cartridge and flushed through a silica gel column with ethylacetate/hexanes. The resulting yellow foam was dissolved in ethylacetate (2 mL) and 10% palladium on carbon (10 mg, 0.009 mmol) wasadded. The slurry was stirred under an atmosphere of hydrogen gas(balloon) for 7 hours. The slurry was filtered through a pad of Celite®with ethyl acetate and concentrated. Purification by flash columnchromatography gave the title compound as a white foam (0.1479 g, 25%):¹H NMR (400 MHz, DMSO-d₆) δ 10.27 (s, 1H), 7.67 (t, J=8.1 Hz, 1H), 7.50(t, J=10.1 Hz, 1H), 7.12 (d, J=8.6 Hz, 1H), 6.73 (d, J=2.7 Hz, 1H), 6.65(dd, J=8.6, 2.7 Hz, 1H), 5.48 (s, 2H), 1.40 (s, 18H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −117.30 (d, J=6.4 Hz), −122.18 (d, J=6.4 Hz); ESIMS m/z 495.6[(M−H)⁻].

Example 86: Preparation of methyl5-((tert-butoxycarbonyl)amino)-2-chlorobenzoate (C362)

To a solution of methyl 5-amino-2-chlorobenzoate (1.00 g, 5.39 mmol) indichloromethane (20 mL) was added di-tert-butyl dicarbonate (1.293 g,5.93 mmol). The reaction mixture was stirred for 72 hours at roomtemperature. Additional di-tert-butyl dicarbonate (0.600 g, 2.75 mmol)was added, and the reaction mixture was allowed to stir for 16 hours.The reaction mixture was washed with aqueous hydrochloric acid (1 N),and the organic layer was concentrated. Purification of the residue byflash column chromatography using 0-30% ethyl acetate/hexane as eluentafforded the title compound as a colorless oil (0.749 g, 49%): ¹H NMR(400 MHz, CDCl₃) δ 7.85 (d, J=2.8 Hz, 1H), 7.49 (dd, J=8.7, 2.8 Hz, 1H),7.35 (d, J=8.7 Hz, 1H), 6.64 (s, 1H), 3.92 (s, 3H), 1.52 (s, 9H); ¹³CNMR (101 MHz, CDCl₃) δ 165.82, 152.38, 137.15, 131.45, 130.25, 127.18,122.35, 120.91, 81.21, 52.46, 28.26; HRMS-ESI (m/z) [M+H]⁺ calcd forC₁₃H₁₆ClNO₄, 285.0768; found, 285.0772.

Example 87: Preparation of methyl5-((tert-butoxycarbonyl)(methyl)amino)-2-chlorobenzoate (C363)

To a solution of methyl 5-((tert-butoxycarbonyl)amino)-2-chlorobenzoate(C362) (0.350 g, 1.225 mmol) in dry N,N-dimethylformamide (6 mL) cooledin an ice bath was added sodium hydride (60% oil immersion, 0.068 g,1.715 mmol). The slurry was stirred for 30 minutes before iodomethane(0.435 g, 3.06 mmol) was added. The reaction mixture was stirredovernight at room temperature. The reaction mixture was quenched withwater and diluted with ethyl acetate. The phases were separated, and theorganic layer was washed four times with 1:1 brine/water. The organiclayer was poured through a phase separator to dry and concentrated underreduced pressure to afford the title compound as a yellow oil (0.340 g,93%): ¹H NMR (300 MHz, CDCl₃) δ 7.76-7.71 (m, 1H), 7.39 (dd, J=8.7, 0.5Hz, 1H), 7.33 (dd, J=8.6, 2.6 Hz, 1H), 3.93 (s, 3H), 3.26 (s, 3H), 1.46(s, 9H); IR (thin film) 2975, 1737. 1702, 1479 cm⁻¹; HRMS-ESI (m/z)[M+H]⁺ calcd for C₁₄H₁₈ClNO₄, 300.0997; found, 300.0994.

Example 88: Preparation of5-((tert-butoxycarbonyl)(methyl)amino)-2-chlorobenzoic acid (C364)

To a solution of methyl5-((tert-butoxycarbonyl)(methyl)amino)-2-chlorobenzoate (C363) (0.340 g,1.134 mmol) in tetrahydrofuran (3.8 mL) and water (1.9 mL) was addedlithium hydroxide (0.109 g, 4.54 mmol). The reaction mixture was stirredvigorously for six hours at room temperature. The reaction mixture wasthen diluted with ethyl acetate and washed twice with hydrochloric acid(1 N). The organic layer was then washed with brine, poured through aphase separator, and concentrated under reduced pressure to afford thetitle compound as a white solid (0.328 g, 100%): ¹H NMR (400 MHz,DMSO-d₆) δ 13.54 (s, 1H), 7.67 (d, J=2.6 Hz, 1H), 7.48 (d, J=8.6 Hz,1H), 7.43 (dd, J=8.7, 2.7 Hz, 1H), 3.19 (s, 3H), 1.40 (s, 9H); ¹³C NMR(101 MHz, DMSO-d₆) δ 153.30, 142.16, 130.47, 128.65, 127.37, 126.93,80.16, 36.54, 27.83; ESIMS m/z 284 ([M−H]⁻).

Example 89: Preparation of tert-butyl (3-fluoro-4-nitrophenyl)carbamate(C365) andtert-butyl-N-((tert-butoxy)carbonyl)-N-(3-fluoro-4-nitrophenyl)carbamate(C366)

To a solution of 3-fluoro-4-nitroaniline (0.500 g, 3.20 mmol) indichloromethane (16.0 mL) was added di-tert-butyl dicarbonate (0.769 g,3.52 mmol) followed by 4-dimethylaminopyridine (0.039 g, 0.320 mmol).The reaction mixture was stirred for 72 hours at room temperature. Thereaction mixture was quenched with water and poured through a phaseseparator. The organic layer was concentrated, and the residue waspurified by flash column chromatography using 0-20% ethylacetate/hexanes as eluent to afford the title compounds. (C366) wasisolated as a yellow solid (0.282 g, 25%): ¹H NMR (400 MHz, CDCl₃) δ8.09 (dd, J=8.8, 8.1 Hz, 1H), 7.15 (dd, J=11.3, 2.2 Hz, 1H), 7.10 (ddd,J=8.8, 2.2, 1.2 Hz, 1H), 1.46 (s, 18H); ¹⁹F NMR (376 MHz, CDCl₃) δ−115.44; ESIMS m/z 379 ([M+Na]⁺). (C365) was isolated as a white solid(0.317 g, 39%): ¹H NMR (400 MHz, CDCl₃) δ 8.05 (dd, J=9.1, 8.3 Hz, 1H),7.61 (dd, J=13.4, 2.4 Hz, 1H), 7.06 (ddd, J=9.2, 2.4, 1.1 Hz, 1H), 6.84(s, 1H), 1.54 (s, 9H); ¹⁹F NMR (376 MHz, CDCl₃) δ −113.29; ESIMS m/z 255([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 89:

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2-fluoro-4-nitrophenyl)carbamate(C367)

Isolated as a yellow solid (0.426 g, 100%): ¹H NMR (400 MHz, CDCl₃) δ8.06 (ddd, J=8.6, 2.5, 1.2 Hz, 1H), 8.02 (dd, J=9.2, 2.4 Hz, 1H), 7.39(dd, J=8.7, 7.4 Hz, 1H), 1.43 (s, 18H); ¹⁹F NMR (376 MHz, CDCl₃) δ−115.99; ESIMS m/z 379 ([M+Na]⁺).

tert-Butyl (2-fluoro-4-nitrophenyl)carbamate (C368)

Isolated as a yellow solid (0.356 g, 43%): ¹H NMR (400 MHz, CDCl₃) δ8.37 (dd, J=9.2, 7.9 Hz, 1H), 8.10-8.02 (m, 1H), 7.98 (dd, J=10.9, 2.5Hz, 1H), 7.00 (s, 1H), 1.55 (s, 9H); ¹⁹F NMR (376 MHz, CDCl₃) δ −129.82;ESIMS m/z 255 ([M−H]⁻).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2,6-difluoro-3-nitrophenyl)carbamate(C369)

Isolated as a white foam (5.2 g, 69%): ¹H NMR (300 MHz, CDCl₃) δ 8.14(ddd, J=9.2, 8.1, 5.5 Hz, 1H), 7.10 (ddd, J=9.7, 8.0, 2.0 Hz, 1H), 1.45(s, 18H); ¹⁹F NMR (376 MHz, CDCl₃) δ −105.95 (dd, J=10.9, 2.7 Hz),−119.53 (d, J=10.6 Hz); ESIMS m/z 397 ([M+Na]⁺).

tert-butyl-N-((tert-butoxy)carbonyl)-N-(2,4-difluoro-5-nitrophenyl)carbamate(C370)

Isolated as a white solid (1.2 g, 56%): ¹H NMR (400 MHz, CDCl₃) δ 8.05(t, J=7.7 Hz, 1H), 7.11 (dd, J=10.2, 8.9 Hz, 1H), 1.46 (s, 18H); ¹⁹F NMR(376 MHz, CDCl₃) δ −105.08 (dd, J=14.8, 2.2 Hz), −111.35 (dd, J=14.6,2.3 Hz); ESIMS m/z 397 ([M+Na]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2,4-difluoro-6-nitrophenyl)carbamate(C371)

Isolated as a brown solid (2.1 g, 88%): ¹H NMR (400 MHz, DMSO-d₆) δ8.14-7.99 (m, 2H), 1.36 (s, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −105.41(d, J=8.4 Hz), −115.11 (d, J=8.4 Hz); ESIMS m/z 374 ([M+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(4-fluoro-2-nitrophenyl)carbamate(C372)

Isolated as a brown solid (2.2 g, 87%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.10(dt, J=8.4, 1.6 Hz, 1H), 7.78-7.68 (m, 2H), 1.33 (s, 18H); ¹⁹F NMR (376MHz, DMSO-d₆) δ −109.89; ESIMS m/z 357 ([M+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3,5-difluoro-2-nitrophenyl)carbamate(C373)

Isolated as a light yellow oil (1.1 g, 51%): ¹H NMR (400 MHz, CDCl₃) δ7.04 (ddd, J=9.7, 8.0, 2.7 Hz, 1H), 6.90 (ddd, J=8.2, 2.7, 2.0 Hz, 1H),1.43 (s, 18H); ¹⁹F NMR (376 MHz, CDCl₃) δ −101.60 (d, J=9.1 Hz), −115.67(d, J=9.4 Hz); ESIMS m/z 273 ([M-C₅H₉O₂+H]⁺).

tert-Butyl (2-methyl-5-nitrophenyl)carbamate (C374)

Isolated as a pale yellow solid product (0.085 g, 85%); mp 137-145° C.;¹H NMR (400 MHz, DMSO-d₆) δ 8.93 (s, 1H), 8.39 (d, J=2.5 Hz, 1H), 7.87(dd, J=8.4, 2.5 Hz, 1H), 7.45 (d, J=8.5 Hz, 1H), 2.33 (s, 3H), 1.50 (s,9H); ESIMS m/z 251 ([M−H]⁻).

tert-Butyl (2-fluoro-5-nitrophenyl)carbamate (C375)

Isolated as a white foam (0.32 g, 20%): ¹H NMR (400 MHz, CDCl₃) δ8.39-8.23 (m, 2H), 7.33 (t, J=8.8 Hz, 1H), 1.47 (s, 9H); ¹⁹F NMR (376MHz, CDCl₃) δ −110.17; ESIMS m/z 256 ([M−H]⁻).

tert-Butyl-N-((tert-butoxy)carbonyl)-(4-fluoro-3-nitrophenyl)carbamate(C376)

Isolated as a yellow oil (1.250 g, 43%): ¹H NMR (400 MHz, DMSO-d₆) δ8.14 (dd, J=6.7, 2.7 Hz, 1H), 7.77 (ddd, J=8.9, 4.0, 2.7 Hz, 1H), 7.63(dd, J=11.0, 8.9 Hz, 1H), 1.39 (s, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ−120.67; ESIMS m/z 379 ([M+Na]*).

tert-Butyl-N-((tert-butoxy)carbonyl)-(2-fluoro-3-nitrophenyl)carbamate(C377)

Isolated as a yellow oil (0.071 g, 3.1%): ¹H NMR (400 MHz, DMSO-d₆) δ8.17 (ddd, J=8.5, 7.0, 1.7 Hz, 1H), 7.90 (ddd, J=8.3, 6.8, 1.7 Hz, 1H),7.49 (td, J=8.2, 1.4 Hz, 1H), 1.39 (s, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆)δ −129.40; ESIMS m/z 379 ([M+Na]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2-fluoro-5-nitrophenyl)carbamate(C378)

Isolated as a white foam (1.50 g, 65%): ¹H NMR (400 MHz, CDCl₃) δ 8.24(ddd, J=9.0, 4.2, 2.8 Hz, 1H), 8.15 (dd, J=6.5, 2.8 Hz, 1H), 7.33-7.26(m, 1H), 1.45 (s, 18H); ¹⁹F NMR (376 MHz, CDCl₃) δ −110.17; ESIMS m/z256 ([M−BOC]⁻).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2,5-difluoro-4-nitrophenyl)carbamate(C379)

Isolated as a white solid (2.1 g, 84%): ¹H NMR (400 MHz, DMSO-d₆) δ8.31(dd, J=9.4, 6.7 Hz, 1H), 8.02 (dd, J=11.5, 6.4 Hz, 1H), 1.40 (s, 18H);¹⁹F NMR (376 MHz, DMSO-d₆) δ −122.00 (d, J=16.1 Hz), −123.68 (d, J=15.8Hz); ESIMS m/z 397 ([M+Na]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-(2,6-difluoro-4-nitrophenyl)carbamate(C380)

Isolated as a light yellow solid (2.0 g, 84%): ¹H NMR (400 MHz, DMSO-d₆)δ 8.33-8.24 (m, 2H), 1.40 (s, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ−115.68; ESIMS m/z 374 ([M−H]⁻).

tert-Butyl (2-fluoro-5-nitrophenyl)(methyl)carbamate (C381)

Isolated as a light yellow foam (0.228 g, 60%): ¹H NMR (400 MHz,DMSO-d₆) δ 8.35 (dd, J=6.7, 2.9 Hz, 1H), 8.22 (ddd, J=9.1, 4.1, 2.9 Hz,1H), 7.59 (t, J=9.4 Hz, 1H), 3.19 (s, 3H), 1.36 (s, 9H); ¹⁹F NMR (376MHz, DMSO-d₆) δ −109.93; ESIMS m/z 270 ([M−H]⁻).

tert-Butyl-methyl(2-methyl-4-nitrophenyl)carbamate (C382)

Isolated as an off-white solid (0.094 g, 65%): mp 98-101° C.; ¹H NMR(500 MHz, CDCl₃) δ 8.12 (d, J=2.5 Hz, 1H), 8.05 (dd, J=8.6, 2.6 Hz, 1H),7.29-7.23 (m, 1H), 3.18 (s, 3H), 2.32 (s, 3H), 1.44 (d, J=86.1 Hz, 9H);¹³C NMR (126 MHz, CDCl₃) δ 154.01, 148.41, 146.25, 137.41, 128.15,125.81, 122.08, 80.82, 36.55, 28.22, 17.91.

tert-Butyl-methyl(2-methyl-5-nitrophenyl)carbamate (C383)

Isolated as a yellow solid (0.74 g, 65%): mp 57-60° C.; ¹H NMR (500 MHz,CDCl³) δ 8.05 (dd, J=8.5, 2.1 Hz, 1H), 7.99 (s, 1H), 7.39 (d, J=8.4 Hz,1H), 3.19 (s, 3H), 2.35-2.31 (m, 7H), 1.44 (d, J=94.3 Hz, 9H); 13C NMR(126 MHz, CDCl₃) δ 154.24, 146.74, 143.89, 143.29, 131.25, 122.74,121.99, 99.98, 80.71, 37.48, 36.65, 28.19, 17.96.

Example 90: Preparation of tert-Butyl(3-fluoro-4-nitrophenyl)(methyl)carbamate (C384)

To a solution of tert-butyl (3-fluoro-4-nitrophenyl)carbamate (C365)(0.310 g, 1.210 mmol) in dry N,N-dimethylformamide (6 mL) cooled in anice bath was added sodium hydride (60% oil dispersion, 0.068 g, 1.694mmol). The slurry was stirred for 30 minutes before iodomethane (0.189mL, 3.02 mmol) was added. The reaction mixture was warmed to roomtemperature and stirred overnight. The reaction mixture was quenchedwith water and diluted with ethyl acetate. The phases were separated,and the organic layer was washed with 1:1 brine/water four times. Theorganic layer was poured through a phase separator to dry and thenconcentrated under reduced pressure to afford the title compound as ayellow oil (0.325 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 8.06 (dd, J=9.1,8.5 Hz, 1H), 7.35 (dd, J=13.3, 2.4 Hz, 1H), 7.24 (ddd, J=9.2, 2.4, 1.2Hz, 1H), 3.34 (s, 3H), 1.52 (s, 9H); ¹⁹F NMR (376 MHz, CDCl₃) δ −115.17;ESIMS m/z 215 ([M-C₄H₉+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 90:

tert-Butyl (2-fluoro-4-nitrophenyl)(methyl)carbamate (C385)

Isolated as a yellow oil (0.359 g, 100%): ¹H NMR (400 MHz, CDCl₃) δ8.15-7.86 (m, 2H), 7.43 (dd, J=8.7, 7.5 Hz, 1H), 3.26 (d, J=1.0 Hz, 3H),1.44 (s, 9H); ¹⁹F NMR (376 MHz, CDCl₃) δ −114.41; EIMS m/z 270.

tert-Butyl methyl (3-methyl-4-nitrophenyl)carbamate (C386)

Isolated as a yellow oil (0.265 g, 100%): ¹H NMR (400 MHz, CDCl₃) δ 8.01(dt, J=8.7, 0.9 Hz, 1H), 7.27 (d, J=1.1 Hz, 2H), 7.26-7.24 (m, 1H), 3.31(s, 3H), 2.62 (s, 3H), 1.50 (s, 9H); 13C NMR (101 MHz, CDCl₃) δ 153.81,147.91, 145.00, 134.74, 127.79, 125.46, 122.33, 81.62, 36.75, 28.26,21.08; ESIMS m/z 211 ([M-C₄H₉+H]⁺).

tert-Butyl (2-methoxy-5-nitrophenyl)(methyl)carbamate (C387)

Isolated as a yellow oil (0.171 g, 100%): ¹H NMR (300 MHz, CDCl₃) δ 8.18(dd, J=9.1, 2.8 Hz, 1H), 8.09 (s, 1H), 6.98 (d, J=9.1 Hz, 1H), 3.96 (s,3H), 3.15 (s, 3H), 1.39 (s, 9H); IR (thin film) 2975, 1699, 1519 cm⁻¹;ESIMS m/z 183 ([M-C₅H₉O₂+H]⁺).

tert-Butyl-methyl(2-methyl-4-nitrophenyl)carbamate (C388)

Isolated as an off-white solid product (0.094 g, 65%): mp 98-101° C.; ¹HNMR (500 MHz, CDCl₃) δ 8.12 (d, J=2.5 Hz, 1H), 8.05 (dd, J=8.6, 2.6 Hz,1H), 7.29-7.23 (m, 1H), 3.18 (s, 3H), 2.32 (s, 3H), 1.44 (d, J=86.1 Hz,9H); ¹³C NMR (126 MHz, CDCl₃) δ 154.01, 148.41, 146.25, 137.41, 128.15,125.81, 122.08, 80.82, 36.55, 28.22, 17.91.

tert-Butyl-methyl(2-methyl-5-nitrophenyl)carbamate (C389)

Isolated as a yellow solid (0.74 g, 65%): mp 57-60° C.; ¹H NMR (500 MHz,CDCl₃) δ 8.05 (dd, J=8.5, 2.1 Hz, 1H), 7.99 (s, 1H), 7.39 (d, J=8.4 Hz,1H), 3.19 (s, 3H), 2.35-2.31 (m, 7H), 1.44 (d, J=94.3 Hz, 9H); ¹³C NMR(126 MHz, CDCl³) δ 154.24, 146.74, 143.89, 143.29, 131.25, 122.74,121.99, 99.98, 80.71, 37.48, 36.65, 28.19, 17.96.

Example 91: Preparation of tert-butyl (4-amino-3-fluorophenyl)(methyl)carbamate (C390)

To a solution of tert-butyl (3-fluoro-4-nitrophenyl)(methyl)carbamate(C384) (0.325 g, 1.203 mmol) in ethyl acetate (10 mL) was added 5%palladium on carbon (0.128 g, 0.060 mmol). The reaction mixture wasstirred vigorously overnight at room temperature under a balloon ofhydrogen. The reaction was filtered through a pad of Celite® and washedwith ethyl acetate. The filtrates were concentrated under reducedpressure to afford the title compound as a red oil (0.225 g, 78%): ¹HNMR (400 MHz, CDCl₃) δ 6.89 (d, J=12.2 Hz, 1H), 6.80 (d, J=8.6 Hz, 1H),6.71 (dd, J=9.7, 8.5 Hz, 1H), 3.67 (s, 2H), 1.43 (s, 9H); ¹⁹F NMR (376MHz, CDCl₃) δ −133.96; ESIMS m/z 185 ([M-C₄H₉+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 91:

N-(4-Amino-3-fluorophenyl)acetamide (C391)

Isolated as a light brown foam (0.460 g, 100%): ¹H NMR (400 MHz,DMSO-d₆) δ 9.68 (s, 1H), 7.38 (dd, J=13.7, 2.3 Hz, 1H), 6.94 (ddd,J=8.5, 2.3, 0.9 Hz, 1H), 6.67 (dd, J=10.1, 8.5 Hz, 1H), 4.85 (s, 2H),1.97 (s, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −133.53; ESIMS m/z 169([M+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(4-amino-2-fluorophenyl)carbamate(C392)

Isolated as a white foam (0.426 g, 100%): ¹H NMR (400 MHz, CDCl₃) δ6.94-6.85 (m, 1H), 6.44-6.40 (m, 1H), 6.39 (d, J=1.8 Hz, 1H), 3.78 (s,2H), 1.42 (s, 18H); ¹⁹F NMR (376 MHz, CDCl₃) δ −121.91; ESIMS m/z 327([M+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(4-amino-3-fluorophenyl)carbamate(C393)

Isolated as a white solid (0.290 g, 100%): ¹H NMR (400 MHz, CDCl₃) δ6.83-6.78 (m, 1H), 6.74-6.71 (m, 2H), 3.75 (s, 2H), 1.43 (s, 18H); ¹⁹FNMR (376 MHz, CDCl₃) δ −134.34; ESIMS m/z 327 ([M+H]⁺).

tert-Butyl (4-amino-2-fluorophenyl)(methyl)carbamate (C394)

Isolated as a colorless oil (0.339 g, 100%): ¹H NMR (400 MHz, CDCl₃) δ6.93 (s, 1H), 6.45-6.34 (m, 2H), 3.73 (s, 2H), 3.14 (s, 3H), 1.36 (s,9H); ¹⁹F NMR (376 MHz, CDCl₃) δ −121.26; ESIMS m/z 241 ([M+H]⁺).

tert-Butyl (4-amino-3-methylphenyl)(methyl)carbamate (C395)

Isolated as a white solid (0.238 g, 100%): ¹H NMR (400 MHz, DMSO-d₆) δ6.78 (d, J=2.5 Hz, 1H), 6.73 (dd, J=8.3, 2.6 Hz, 1H), 6.53 (d, J=8.3 Hz,1H), 4.77 (s, 2H), 3.05 (s, 3H), 2.02 (s, 3H), 1.35 (s, 9H); IR (thinfilm) 3374, 2925, 1680, 1630, 1511 cm⁻¹; ESIMS m/z 237 ([M+H]⁺).

tert-Butyl (5-amino-2-methoxyphenyl)(methyl)carbamate (C396)

Isolated as a light brown oil (0.150 g, 99%): ¹H NMR (300 MHz, DMSO-d₆)δ 6.74 (d, J=8.5 Hz, 1H), 6.43 (dd, J=8.6, 2.8 Hz, 1H), 6.39 (d, J=2.7Hz, 1H), 4.67 (s, 2H), 3.65 (s, 3H), 2.96 (s, 3H), 1.29 (s, 9H); IR(thin film) 3351, 2975, 1683, 1630, 1509 cm⁻¹; ESIMS m/z 153([M-C₅H₉O₂+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(3-amino-2,6-difluorophenyl)carbamate(C397)

Isolated as a white solid (5.06 g, 100%): ¹H NMR (400 MHz, DMSO-d₆) δ6.87 (td, J=9.3, 1.7 Hz, 1H), 6.74 (td, J=9.4, 5.7 Hz, 1H), 5.12 (s,2H), 1.39 (s, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −137.96 (d, J=3.7 Hz),−141.10 (d, J=3.7 Hz); ESIMS m/z 244 ([M−BOC]⁻).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(5-amino-2,4-difluorophenyl)carbamate(C398)

Isolated as a cream colored solid (1.05 g, 88%): ¹H NMR (400 MHz, CDCl₃)δ 6.82 (dd, J=10.5, 9.3 Hz, 1H), 6.60 (dd, J=9.1, 7.5 Hz, 1H), 3.59 (s,2H), 1.43 (s, 18H); ¹⁹F NMR (376 MHz, CDCl₃) δ −131.04 (t, J=2.2 Hz),−131.38 (d, J=2.0 Hz); ESIMS m/z 245 ([M-C₅H₉O₂+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2-amino-4,6-difluorophenyl)carbamate(C399)

Isolated as a light orange solid (1.3 g, 61%): mp 102-107° C.; ¹H NMR(300 MHz, DMSO-d₆) δ 6.36-6.21 (m, 2H), 5.72 (s, 2H), 1.36 (s, 18H);ESIMS m/z 345 ([M+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2-amino-4-fluorophenyl)carbamate(C400)

Isolated as an off-white solid (1.8 g, 80%): mp 104-115° C.; ¹H NMR (300MHz, DMSO-d₆) δ 6.94-6.79 (m, 1H), 6.44 (dd, J=11.3, 2.9 Hz, 1H), 6.26(td, J=8.5, 2.9 Hz, 1H), 5.23 (s, 2H), 1.36 (s, 18H); ESIMS m/z 327([M+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(2-amino-3,5-difluorophenyl)carbamate(C401)

Isolated as a white solid (0.90 g, 98%): ¹H NMR (400 MHz, DMSO-d₆) δ7.07 (ddd, J=11.6, 8.9, 2.9 Hz, 1H), 6.79 (ddd, J=9.3, 2.9, 1.9 Hz, 1H),4.87 (s, 2H), 1.36 (s, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −128.55,−129.76; ESIMS m/z 245 ([M-C₅H₉O₂+H]⁺).

tert-Butyl (5-amino-2-methylphenyl)carbamate (C402)

Isolated as a light pink solid (0.06 g, 90%): ¹H NMR (500 MHz, DMSO-d₆)δ 8.17 (s, 1H), 6.76 (d, J=8.1 Hz, 1H), 6.61 (d, J=2.4 Hz, 1H), 6.25(dd, J=8.0, 2.3 Hz, 1H), 4.81 (s, 2H), 2.00 (s, 3H), 1.44 (s, 9H); ¹³CNMR (126 MHz, DMSO-d₆) δ 153.92, 147.16, 137.23, 130.67, 118.69, 111.13,78.73, 28.66, 17.35; IR (thin film) 3425, 3314, 2981, 2928, 1695, 1621,1582, 1531 cm⁻¹.

tert-Butyl (4-amino-2-methylphenyl)(methyl)carbamate (C403)

Isolated as a brown gel (0.035 g, 58%): ¹H NMR (500 MHz, DMSO-d₆) δ 6.74(d, J=8.4 Hz, 1H), 6.38 (d, J=2.6 Hz, 1H), 6.34 (dd, J=8.3, 2.7 Hz, 1H),4.96 (d, J=7.6 Hz, 2H), 2.98 (d, J=19.9 Hz, 3H), 1.98 (d, J=11.3 Hz,3H), 1.35 (d, J=84.4 Hz, 9H); ¹³C NMR (126 MHz, DMSO-d₆) δ 155.12,147.74, 135.12, 131.46, 127.85, 115.69, 112.47, 78.63, 37.53, 28.48,17.72; IR (thin film) 3357, 2975, 2928, 1677, 1506 cm⁻¹.

tert-Butyl (5-amino-2-methylphenyl)(methyl)carbamate (C404)

Isolated as a pale brown solid (0.037 g, 77%): ¹H NMR (500 MHz, DMSO-d₆)δ 6.86 (d, J=8.1 Hz, 1H), 6.39 (d, J=7.4 Hz, 1H), 6.33 (s, 1H), 4.90 (s,2H), 2.99 (d, J=17.0 Hz, 3H), 1.95 (d, J=8.1 Hz, 3H), 1.36 (d, J=81.4Hz, 9H); ¹³C NMR (126 MHz, DMSO-d₆) δ 154.52, 147.78, 142.83, 130.99,121.55, 113.50, 112.90, 78.94, 37.15, 28.46, 16.66; IR (thin film) 3461,3366, 2924, 1664, 1616, 1513 cm⁻¹.

tert-Butyl (5-amino-2-fluorophenyl)(methyl)carbamate (C405)

Isolated as an off-white solid (0.170 g, 80%): ¹H NMR (300 MHz, DMSO-d₆)δ 6.87 (dd, J=10.4, 8.6 Hz, 1H), 6.50-6.36 (m, 2H), 5.00 (s, 2H), 3.04(s, 3H), 1.34 (s, 9H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −138.52; ESIMS m/z241 ([M+H]⁺).

tert-Butyl (4-amino-3-methylphenyl)carbamate (C406)

Isolated as a light pink solid (12.4 g, 87%): ¹H NMR (400 MHz, DMSO-d₆)δ 8.72 (s, 1H), 7.01 (s, 1H), 6.93 (d, J=8.5 Hz, 1H), 6.49 (d, J=8.4 Hz,1H), 4.49 (s, 2H), 2.00 (s, 3H), 1.44 (s, 9H); ESIMS m/z 223 ([M+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl(4-amino-2,6-difluorophenyl)carbamate (C407)

Isolated as an off-white solid (1.5 g, 73%): ¹H NMR (400 MHz, DMSO-d₆) δ6.28-6.18 (m, 2H), 5.83 (s, 2H), 1.37 (s, 18H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −122.91; ESIMS m/z 345 ([M+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-(3-amino-2-fluorophenyl)carbamate(C408)

Isolated as an light pink solid (0.047 g, 71%): ¹H NMR (400 MHz,DMSO-d₆) δ 6.83 (td, J=8.0, 1.3 Hz, 1H), 6.71 (td, J=8.2, 1.7 Hz, 1H),6.37 (ddd, J=8.2, 6.8, 1.6 Hz, 1H), 5.22 (s, 2H), 1.39 (s, 18H); ¹⁹F NMR(376 MHz, DMSO-d₆) δ −144.87; ESIMS m/z 327 ([M+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-(3-amino-4-fluorophenyl)carbamate(C409)

Isolated as a light pink solid (1.0 g, 89%): ¹H NMR (400 MHz, DMSO-d₆) δ7.03-6.90 (m, 1H), 6.54 (dd, J=8.1, 2.6 Hz, 1H), 6.29 (ddd, J=8.5, 4.0,2.7 Hz, 1H), 5.22 (s, 2H), 1.39 (s, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ−136.69; ESIMS m/z 327 ([M+H]⁺).

tert-Butyl-N-((tert-butoxy)carbonyl)-(5-amino-2-fluorophenyl)carbamate(C410)

Isolated as a grey solid (1.048 g, 68%): ¹H NMR (400 MHz, DMSO-d₆) δ6.91 (dd, J=10.1, 8.8 Hz, 1H), 6.49 (ddd, J=8.8, 4.1, 2.8 Hz, 1H), 6.39(dd, J=6.7, 2.8 Hz, 1H), 5.03 (s, 2H), 1.39 (s, 18H): ¹⁹F NMR (376 MHz,DMSO-d₆) δ −139.75; ESIMS m/z 226 ([M−BOC]⁻).

tert-Butyl-N-((tert-butoxy)carbonyl)-N-(4-amino-2,5-difluorophenyl)carbamate(C411)

Isolated as a grey solid (1.5 g, 83%): ¹H NMR (400 MHz, DMSO-d₆) δ7.09-6.99 (m, 1H), 6.56 (dd, J=11.8, 8.0 Hz, 1H), 5.55 (s, 2H), 1.37 (d,J=1.4 Hz, 18H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −128.64 (d, J=13.9 Hz),−139.89 (d, J=13.8 Hz); ESIMS m/z 345 ([M−H]⁻).

Example 92: Preparation of N⁴-benzyl-3,5-difluoropyridine-2,4-diamine(C412)

A suspension of 3,5-difluoro-4-iodopyridin-2-amine (200 mg, 0.781 mmol),tris(dibenzylideneacetone)dipalladium(O) (71.5 mg, 0.078 mmol),2,2′-bis(diphenylphosphanyl)-1,1′-binaphthalene (97 mg, 0.156 mmol),sodium 2-methylpropan-2-olate (90 mg, 0.938 mmol), and benzylamine (112μL, 0.938 mmol) in toluene (3.9 mL) was evacuated under vacuum andbackfilled with nitrogen three times. The reaction mixture was thensealed under a blanket of nitrogen and heated via microwave irradiationto 130° C. for 2 hours. The reaction mixture was diluted with ethylacetate and quenched with aqueous sodium hydroxide (2 N). The layerswere separated, and the aqueous phase was extracted with ethyl acetatethree times. The combined organic phase was washed with brine, driedover sodium sulfate and filtered. The solvent was evaporated.Purification by flash column chromatography using 0-100% ethyl acetatein hexanes as the eluent afforded the title compound as a yellow solid(0.093 g, 51%): ¹H NMR (300 MHz, CDCl₃) δ 7.56 (dd, J=2.9, 1.0 Hz, 1H),7.42-7.23 (m, 5H), 4.62 (dt, J=6.3, 1.4 Hz, 2H), 4.36 (t, J=9.9 Hz, 3H);ESIMS m/z 236 ([M+H]⁺); IR (thin film) 3307, 3181, 3030, 2924, 1631,1577, 1530, 1475, 1453 cm⁻¹.

Example 93: Preparation of tert-butyl(6-amino-4-(trifluoromethyl)pyridin-2-yl)carbamate (C413)

A solution of di-tert-butyl dicarbonate (3.93 g, 18.00 mmol) intetrahydrofuran (10 mL) was added dropwise to a solution of4-(trifluoromethyl)pyridine-2,6-diamine (3.19 g, 18 mmol) intetrahydrofuran (20 mL) at room temperature. Upon completion of theaddition, the reaction mixture was fitted with a reflux condenser andheated to 60° C. overnight. The solvent was evaporated. Purification byflash column chromatography using 5-10% ethyl acetate in dichloromethaneas the eluent afforded the title compound as a thick, pale yellow oil(2.80 g, 56%): ¹H NMR (400 MHz, CDCl₃) δ 7.86 (s, 1H), 7.47 (s, 1H),6.35 (s, 1H), 4.71 (s, 2H), 1.52 (s, 9H); ¹⁹F NMR (376 MHz, CDCl₃) δ−65.27; ESIMS m/z 278 ([M+H]⁺).

Example 94: Preparation of 3,5-difluoropyridine-2,4-diamine (C414)

2,3,5-Trifluoropyridin-4-amine (0.200 g, 1.351 mmol) was suspended inammonium hydroxide (5 mL, 128 mmol) in a high pressure reactor equippedwith a magnetic stir bar. The reactor was sealed and, with stirring,heated to 120° C. for 24 hours and then to 160° C. for an additional 24hours. The reaction mixture was cooled to room temperature and extractedwith ethyl acetate four times. The combined organic layers were driedover magnesium sulfate, filtered, and concentrated under reducedpressure to afford the title compound as a light brown solid (0.163 g,83%): ¹H NMR (400 MHz, DMSO-d₆) δ 7.46 (d, J=2.0 Hz, 1H), 5.90 (s, 2H),5.47 (s, 2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −160.20 (d, J=5.4 Hz),−160.96 (d, J=5.4 Hz); EIMS m/z 145.

Example 95: Preparation of 1-ethyl-1H-indol-5-amine (C415)

Ethyl iodide (289 mg, 1.85 mmol) was added in one portion to a stirredsolution of 5-nitro-1H-indole (250 mg, 1.542 mmol) and potassiumcarbonate (426 mg, 3.08 mmol) in DMF (5 mL) at room temperature. Theresulting brown suspension was poured into water (50 mL), and theresulting precipitate was collected by vacuum filtration and dried invacuo at 40° C. to a constant weight. 1-Ethyl-5-nitro-1H-indole wasisolated as a pale yellow solid (0.220 g, 71.3%): ¹H NMR (400 MHz,DMSO-d₆) δ 8.57 (d, J=2.3 Hz, 1H), 8.03 (dd, J=9.1, 2.3 Hz, 1H),7.74-7.65 (m, 2H), 6.76 (d, J=3.2 Hz, 1H), 4.30 (q, J=7.2 Hz, 2H), 1.38(t, J=7.2 Hz, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ 140.61, 138.27, 131.90,127.33, 117.53, 116.23, 110.18, 103.59, 40.85, 40.17, 39.96, 39.75,39.54, 39.33, 39.13, 38.92, 15.34; ESIMS m/z 191 ([M+H]⁺).

Palladium hydroxide (10% on carbon, 78 mg, 0.055 mmol) was added in oneportion to a stirred solution of 1-ethyl-5-nitro-1H-indole (210 mg,1.104 mmol) in ethyl acetate (50 mL). A balloon filled with hydrogen wasattached to the flask, and the vessel was filled with hydrogen,evacuated, and refilled with hydrogen. The heterogenous mixture wasstirred at room temperature for 16 hours, after which the reactionmixture was filtered through a pad of Celite®, and the filtrate wasconcentrated under vacuum on a rotary evaporator. Purification by silicagel column chromatography gave 1-ethyl-1H-indol-5-amine as an amber oil(0.144 g, 80%): ¹H NMR (400 MHz, CDCl₃) δ 7.14 (d, J=8.5 Hz, 1H), 7.02(d, J=3.1 Hz, 1H), 6.92 (d, J=2.2 Hz, 1H), 6.67 (dd, J=8.6, 2.2 Hz, 1H),6.29 (dd, J=3.1, 0.8 Hz, 1H), 4.08 (q, J=7.3 Hz, 2H), 3.46 (s, 2H), 1.42(t, J=7.3 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 139.18, 130.88, 129.52,127.33, 112.39, 109.81, 105.85, 99.67, 77.38, 77.26, 77.06, 76.75,41.00, 15.46. ESIMS m/z 161 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 95:

1-(2-Fluoroethyl)-1H-indol-5-amine (C416)

Isolated as an amber oil (0.120 g, 92%): ESIMS m/z 179 ([M+H]⁺).

Example 96: Preparation oftrans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane carboxylic acid(C1)

Sodium permanganate (40% aqueous) (84 g, 236 mmol) was added dropwise toa stirred mixture oftrans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde(C437) (58.7 g, 196 mmol) in acetone (982 mL) at 15° C. The resultingmixture was stirred at 20° C. for 2 hours. The reaction mixture wasdiluted with isopropyl alcohol (20 mL) and concentrated to remove theacetone. Celite® and aqueous hydrochloric acid (1 N, 295 mL, 295 mmol)were added to the brown residue. The resulting mixture was diluted withethyl acetate (500 mL) and filtered through Celite®. The filtrate waswashed with brine (200 mL). The organic layer was dried over sodiumsulfate, filtered and concentrated. The resulting slurry was dilutedwith heptane (˜200 mL) and allowed to solidify at 20° C. The solid wascollected, washed with heptane and dried to afford the title product asa white solid (54.68 g, 91%): ¹H NMR (300 MHz, CDCl₃) δ 7.36 (t, J=1.9Hz, 1H), 7.17 (dd, J=1.9, 0.7 Hz, 2H), 3.48-3.37 (m, 1H), 2.87 (d, J=8.3Hz, 1H); ¹³C NMR (400 MHz, CDCl₃) δ 135.44, 135.28, 128.66, 127.30,39.68, 36.88; ESIMS m/z=298.9 ([M−H])⁻.

The following compounds were prepared in like manner to the procedureoutlined in Example 96:

trans-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxylicacid (C2)

Isolated as a white solid (2.78 g, 95%): ¹H NMR (400 MHz, DMSO-d₆) δ13.41 (s, 1H), 7.81 (d, J=0.6 Hz, 2H), 3.62 (d, J=8.6 Hz, 1H), 3.52 (d,J=8.6 Hz, 1H); ESIMS m/z 332 ([M−H]⁻).

trans-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxylic acid(C3)

Isolated as a white solid (124 g, 82%): mp 133-135° C.: ¹H NMR (500 MHz,DMSO-d₆) δ 13.39 (s, 1H), 7.76 (d, J=2.0 Hz, 1H), 7.64 (d, J=8.3 Hz,1H), 7.44 (dd, J=8.4, 2.1 Hz, 1H), 3.49 (s, 2H). ¹³C NMR (126 MHz,DMSO-d₆) δ 166.34, 133.35, 130.47, 130.33, 130.09, 129.77, 128.81,61.43, 37.00, 36.06.

trans-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylicacid (C16)

Isolated as a white solid (165 g, 71%): ¹H NMR (400 MHz, CDCl₃) δ 11.57(s, 1H), 7.42 (dd, J=8.2, 7.6 Hz, 1H), 7.11-6.98 (m, 2H), 3.46 (d, J=8.2Hz, 1H), 2.85 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −114.07;ESIMS m/z 282 ([M−H]⁻).

In another preparation, isolated as a white powder (10.385 g, 77%):119-121° C.; ¹H NMR (400 MHz, CDCl₃) δ 11.83 (s, 1H), 7.32 (d, J=6.9 Hz,1H), 7.16 (d, J=6.7 Hz, 2H), 3.45 (d, J=8.3 Hz, 1H), 2.85 (d, J=8.3 Hz,1H); ¹³C NMR (101 MHz, CDCl₃) δ 172.18, 159.26, 156.77, 130.95, 129.26,129.22, 128.57, 128.50, 121.52, 121.34, 116.94, 116.73, 61.59, 39.64,37.30; ¹⁹F NMR (376 MHz, CDCl₃) δ −115.16; ESIMS m/z 281 [(M−H)⁻].

trans-2,2-Dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropane-1-carboxylicacid (C417)

Isolated as an off-white solid (1.33 g, 96%): mp 161-164° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 13.35 (s, 1H), 7.63 (s, 2H), 3.83 (s, 3H), 3.52 (d,J=8.6 Hz, 1H), 3.45 (d, J=8.6 Hz, 1H); ¹³C NMR (126 MHz, DMSO-d₆) δ166.81, 151.02, 131.07, 129.63, 128.03, 61.93, 60.52, 37.22, 36.54;ESIMS m/z 329 [(M−H)⁻].

trans-2,2-Dichloro-3-(3-chloro-5-cyanophenyl)cyclopropane-1-carboxylicacid (C418)

Isolated as a white solid (2.92 g, 60%): mp: 173-175° C.; ¹H NMR (500MHz, DMSO-d₆) δ 13.42 (s, 1H), 8.03 (t, J=1.7 Hz, 1H), 7.98 (t, J=1.9Hz, 2H), 3.65 (d, J=8.6 Hz, 1H), 3.57 (d, J=8.6 Hz, 1H); ESIMS m/z 290([M]).

trans-2,2-Dichloro-3-(4-nitrophenyl)cyclopropane-1-carboxylic acid(C419)

Isolated as a pink solid (0.158 g, 48%): ¹H NMR (4 MHz, CDCl₃) δ 8.26(d, J=8.3 Hz, 2H), 7.47 (d, J=8.4 Hz, 2H), 3.57 (d, J=8.3 Hz, 1H), 2.98(d, J=8.3 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 171.34, 147.88, 139.21,129.75, 123.85, 61.33, 40.14, 37.43; IR (thin film) 2923, 2603, 1709,1601, 1520, 1446 cm⁻¹; ESIMS m/z 273.9 [(M−H)⁻].

trans-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylicacid (C420)

Isolated as a white powder (10.385 g, 77%): mp 119-121° C.; ¹H NMR (400MHz, CDCl₃) δ 11.83 (s, 1H), 7.32 (d, J=6.9 Hz, 1H), 7.16 (d, J=6.7 Hz,2H), 3.45 (d, J=8.3 Hz, 1H), 2.85 (d, J=8.3 Hz, 1H); ¹³C NMR (101 MHz,CDCl₃) δ 172.18, 159.26, 156.77, 130.95, 129.26, 129.22, 128.57, 128.50,121.52, 121.34, 116.94, 116.73, 61.59, 39.64, 37.30; ¹⁹F NMR (376 MHz,CDCl₃) δ −115.16; ESIMS m/z 281 [(M−H)⁻].

trans-2,2-Dichloro-3-(3,4-difluorophenyl)cyclopropane-1-carboxylic acid(C421)

Isolated as a white solid (1.44 g, 67%): ¹H NMR (400 MHz, CDCl₃) δ 8.69(s, 1H), 7.18 (dt, J=9.9, 8.3 Hz, 1H), 7.10 (ddd, J=10.8, 7.3, 2.3 Hz,1H), 7.01 (ddt, J=8.1, 3.8, 1.7 Hz, 1H), 3.44 (dd, J=8.4, 1.0 Hz, 1H),2.83 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −136.40, −136.46,−137.42, −137.48; ESIMS m/z 266 ([M−H]⁻).

trans-3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxylicacid (C422)

Isolated as a white solid (1.05 g, 63%): ¹H NMR (400 MHz, CDCl₃) δ8.07-7.63 (m, 1H), 7.58-7.42 (m, 2H), 7.17 (dd, J=8.3, 2.1 Hz, 1H), 3.43(d, J=8.3 Hz, 1H), 2.86 (d, J=8.3 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ171.46, 134.71, 133.88, 132.43, 130.42, 128.70, 122.73, 77.33, 77.22,77.01, 76.69, 61.51, 39.50, 37.21; ESIMS m/z 343 ([M−H]⁻).

trans-2,2-Dichloro-3-(3,4-dibromophenyl)cyclopropane-1-carboxylic acid(C423)

Isolated as a white solid (0.488 g, 57%): ¹H NMR (400 MHz, CDCl₃) δ 8.85(s, 1H), 7.77-7.47 (m, 2H), 7.08 (ddd, J=8.3, 2.1, 0.7 Hz, 1H),3.57-3.25 (m, 1H), 2.86 (d, J=8.3 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ171.54, 133.82, 133.78, 133.08, 128.78, 125.13, 124.98, 77.33, 77.22,77.01, 76.70, 61.41, 39.59, 37.14, 0.01; ESIMS m/z 387 ([M−H]⁻).

trans-2,2-Dichloro-3-(3-fluoro-4-(trifluoromethyl)phenyl)cyclopropane-1-carboxylicacid (C424)

Isolated as a waxy tan solid (4.09 g, 68.7%): ¹H NMR (400 MHz, CDCl₃) δ7.83 (s, 1H), 7.63 (t, J=7.7 Hz, 1H), 7.23-7.04 (m, 2H), 3.51 (d, J=8.3Hz, 1H), 2.92 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −61.40,−61.43, −113.24, −113.27; ESIMS m/z 316 ([M−H]⁻).

trans-3-(4-Bromo-3-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxylicacid (C425)

Isolated as a white solid (0.41 g, 42.1%): ¹H NMR (400 MHz, CDCl₃) δ8.04 (s, 1H), 7.57 (dd, J=8.2, 7.1 Hz, 1H), 7.00 (ddd, J=33.6, 8.7, 2.1Hz, 2H), 3.43 (d, J=8.3 Hz, 1H), 2.85 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376MHz, CDCl₃) δ −106.06; ESIMS m/z 327 ([M−H]⁻).

trans-3-(3-Bromo-4-(trifluoromethyl)-2,2-dichlorophenyl)cyclopropane-1-carboxylicacid (C426)

Isolated as a white solid (0.55 g, 53.8%): ¹H NMR (400 MHz, CDCl₃) δ7.78-7.57 (m, 2H), 7.42-7.29 (m, 1H), 3.50 (d, J=8.3 Hz, 1H), 2.93 (d,J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −62.66, −62.67, −62.81; ESIMSm/z 377 ([M−H]⁻).

trans-3-(4-Bromo-3-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxylicacid (C427)

Isolated as a white solid (1.21 g, 51%): ¹H NMR (400 MHz, CDCl₃) δ 10.87(s, 1H), 7.74 (d, J=8.3 Hz, 1H), 7.58 (d, J=2.2 Hz, 1H), 7.30 (dd,J=8.3, 2.2 Hz, 1H), 3.49 (d, J=8.3 Hz, 1H), 2.91 (d, J=8.3 Hz, 1H); ¹⁹FNMR (376 MHz, CDCl₃) δ −62.77, −62.78; ESIMS m/z 377 ([M−H]⁻).

trans-2,2-Dichloro-3-(3-chloro-4-(trifluoromethyl)phenyl)cyclopropane-1-carboxylicacid (C428)

Isolated as a white solid (0.778 g, 43.4%): ¹H NMR (400 MHz, CDCl₃) δ9.72 (s, 1H), 7.71 (d, J=8.2 Hz, 1H), 7.53-7.39 (m, 1H), 7.35-7.19 (m,1H), 3.50 (d, J=8.3 Hz, 1H), 2.93 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz,CDCl₃) δ −62.63; ESIMS m/z 332 ([M−H]⁻).

trans-2,2-Dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylicacid (C429)

Isolated as a white solid (2.02 g, 43%): ¹H NMR (400 MHz, CDCl₃) δ7.96-7.51 (m, 3H), 7.39 (dd, J=8.3, 2.2 Hz, 1H), 3.50 (d, J=8.3 Hz, 1H),2.90 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −62.75, −62.75; ESIMSm/z 332 ([M−H]⁻).

trans-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxylicacid (C430)

Isolated as a white solid (0.850 g, 43.9%): ¹H NMR (400 MHz, CDCl₃) δ8.47 (s, 1H), 7.47 (ddd, J=6.3, 2.3, 0.7 Hz, 1H), 7.32-7.08 (m, 2H),3.44 (dd, J=8.3, 1.0 Hz, 1H), 2.84 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz,CDCl₃) δ −107.16; ESIMS m/z 327 ([M−H]⁻).

trans-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-carboxylicacid (C431)

Isolated as a white solid (3.08 g, 66.9%): ¹H NMR (400 MHz, CDCl₃) δ8.18 (s, 1H), 7.64-7.39 (m, 2H), 7.24 (t, J=9.3 Hz, 1H), 3.50 (dd,J=8.4, 1.0 Hz, 1H), 2.89 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−61.48, −61.51, −114.23, −114.26, −114.29; ESIMS m/z 316 ([M−H]⁻).

trans-2,2-Dichloro-3-(4-chloro-3-fluorophenyl)cyclopropane-1-carboxylicacid (C432)

Isolated as a white solid (0.96 g, 36.2%): ¹H NMR (400 MHz, CDCl₃) δ11.57 (s, 1H), 7.42 (dd, J=8.2, 7.6 Hz, 1H), 7.11-6.98 (m, 2H), 3.46 (d,J=8.2 Hz, 1H), 2.85 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−114.07; ESIMS m/z 282 ([M−H]⁻).

trans-2,2-Dichloro-3-(3,5-difluorophenyl)cyclopropane-1-carboxylic acid(C433)

Isolated as a clear colorless oil (1.55 g, 28.9%): ¹H NMR (400 MHz,CDCl₃) δ 10.44 (s, 1H), 6.82 (qd, J=6.4, 2.3 Hz, 3H), 3.44 (d, J=8.3 Hz,1H), 2.86 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −108.49,−108.69, −108.82, −109.85; ESIMS m/z 266 ([M−H]⁻).

trans-2,2-Dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-carboxylicacid (C434)

Isolated as a white solid (3.7 g, 54.7%): ¹H NMR (400 MHz, CDCl₃) δ11.40 (s, 1H), 7.42-7.27 (m, 2H), 7.20 (dt, J=8.9, 2.0 Hz, 1H), 3.53 (d,J=8.3 Hz, 1H), 2.93 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−62.86, −109.49; ESIMS m/z 316 ([M−H]⁻).

trans-3-(3-Bromo-5-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxylicacid (C435)

Isolated as a white solid (0.76 g, 47%): ¹H NMR (400 MHz, CDCl₃) δ 11.06(s, 1H), 7.36-7.14 (m, 2H), 7.03-6.87 (m, 1H), 3.45 (d, J=8.3 Hz, 1H),2.87 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −109.73, −109.73;ESIMS m/z 327 ([M−H]⁻).

trans-3-(3-Bromo-5-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxylicacid (C436)

Isolated as a tan solid (0.375 g, 31%): ¹H NMR (400 MHz, CDCl₃) δ 10.52(s, 1H), 7.77 (s, 1H), 7.62 (d, J=1.8 Hz, 1H), 7.46 (s, 1H), 3.52 (d,J=8.2 Hz, 1H), 2.93 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−62.84; ESIMS m/z 377 ([M−H]⁻).

Example 97: Preparation oftrans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclo-propane-1-carbaldehyde(C437)

Aqueous hydrochloric acid (2 N, 237 mL) was added to a stirred solutionof1,3-dichloro-5-((trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzene(C443) (85.7 g, 227 mmol) in acetonitrile (1184 mL). The mixture wasstirred at 20° C. for 16 hours. The resulting mixture was diluted withwater (200 mL) and concentrated to remove the acetonitrile. Theresulting aqueous mixture was extracted with hexanes (600 mL). Theorganic layer was washed water (300 mL), dried over anhydrous sodiumsulfate, filtered and concentrated. The crude product was purified byflash column chromatography using 0-20% ethyl acetate/hexanes as eluentto afford the title product as a yellow oil (58.7 g, 86%, purity 95%):¹H NMR (400 MHz, CDCl₃) δ 9.54 (d, J=4.0 Hz, 1H), 7.46-7.09 (m, 3H),3.51 (d, J=8.0 Hz, 1H), 2.92 (dd, J=8.0, 4.0 Hz, 1H); ¹³C NMR (126 MHz,CDCl₃) δ 193.41, 135.33, 135.09, 128.78, 127.34, 42.89, 39.31; IR (thinfilm) 3078, 2847, 1714, 1590, 1566, 1417, 1387.

The following compounds were prepared in like manner to the procedureoutlined in Example 97:

trans-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carbaldehyde(C438)

Isolated as orange oil (143 g, 98%): ¹H NMR (400 MHz, CDCl₃) δ 9.53 (d,J=4.1 Hz, 1H), 7.47 (d, J=8.3 Hz, 1H), 7.37 (dd, J=2.2, 0.7 Hz, 1H),7.12 (ddd, J=8.3, 2.2, 0.7 Hz, 1H), 3.51 (dd, J=7.9, 0.8 Hz, 1H), 2.90(dd, J=8.0, 4.1 Hz, 1H).

trans-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carbaldehyde(C439)

Isolated as a yellow solid (2.8 g, 69%): ¹H NMR (400 MHz, CDCl₃) δ 9.55(d, J=3.9 Hz, 1H), 7.30 (d, J=0.7 Hz, 2H), 3.48 (dt, J=8.0, 0.8 Hz, 1H),2.92 (dd, J=7.9, 3.9 Hz, 1H).

trans-2,2-Dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropane-1-carbaldehyde(C440)

Isolated as a light-yellow oil (1.346 g, 74%): ¹H NMR (400 MHz, CDCl₃)(9.52 (d, J=4.0 Hz, 1H), 7.22 (s, 2H), 3.90 (s, 3H), 3.48 (d, J=8.0 Hz,1H), 2.91 (dd, J=8.0, 4.0 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 191.67,150.58, 127.74, 127.54, 127.35, 59.76, 58.94, 41.14, 37.13; EIMS m/z314.

trans-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carbaldehyde(C441)

Isolated as orange oil (230 g, 97%): ¹H NMR (300 MHz, CDCl₃) δ 9.52 (d,J=4.2 Hz, 1H), 7.36-7.30 (m, 1H), 7.19-7.16 (m, 1H), 7.15 (d, J=1.2 Hz,1H), 3.51 (dt, J=7.9, 0.7 Hz, 1H), 2.88 (dd, J=7.9, 4.2 Hz, 1H).

In another preparation, isolated as a yellow oil (12.496 g, 71%): ¹H NMR(400 MHz, CDCl₃) δ 9.52 (d, J=4.1 Hz, 1H), 7.33 (d, J=7.2 Hz, 1H), 7.16(dd, J=6.8, 1.0 Hz, 2H), 3.53 (d, J=7.9 Hz, 1H), 2.90 (dd, J=7.9, 4.1Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 193.77, 159.27, 156.78, 131.03,129.04, 129.00, 128.66, 128.59, 121.49, 121.31, 116.95, 116.74, 61.68,43.10, 39.25; ¹⁹F NMR (376 MHz, CDCl₃) δ −115.01; EIMS m/z 266.

3-Chloro-5-(trans-2,2-dichloro-3-formylcyclopropyl)benzonitrile (C442)

Isolated as yellow solid (2.9 g, 77%): ¹H NMR (300 MHz, CDCl₃) δ 9.59(d, J=3.6 Hz, 1H), 7.65 (ddd, J=1.9, 1.4, 0.5 Hz, 1H), 7.52 (td, J=1.8,0.7 Hz, 1H), 7.48 (td, J=1.5, 0.7 Hz, 1H), 3.56 (dq, J=8.0, 0.6 Hz, 1H),2.98 (dd, J=8.0, 3.7 Hz, 1H).

Example 98: Preparation of1,3-dichloro-5-(trans-2,2-dichloro-3-(diethoxy-methyl)cyclopropyl)benzene(C443)

A 1 L 4-neck flask equipped with a mechanical stirrer, condenser,temperature probe and nitrogen inlet was charged with(E)-1,3-dichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene (C449) (40 g, 138mmol) and CHCl₃ (447 mL). Tetrabutylammonium hexafluorophosphate(V)(1.081 g, 2.76 mmol) was added. The light yellow solution was heated to45° C. With vigorous stirring (˜400 rpm), aqueous sodium hydroxide (50%,182 mL) was added dropwise via addition funnel (over 1 hour). After 20hours, the mixture was allowed to cool. The mixture was diluted withhexane (200 mL). The organic top layer was decanted (off the aqueouslower suspension) through Celite®, washing the filtercake with hexane(200 mL). The filtrate was washed with brine (˜200 mL), dried oversodium sulfate, filtered and concentrated to provide the title compoundas a brown oil (50.2 g, 97%, purity 95%): ¹H NMR (300 MHz, CDCl₃) δ 7.31(t, J=1.9 Hz, 1H), 7.15 (dd, J=1.9, 0.7 Hz, 2H), 4.59 (d, J=6.2 Hz, 1H),3.80-3.57 (m, 4H), 2.77 (d, J=8.5 Hz, 1H), 2.25 (dd, J=8.5, 6.2 Hz, 1H),1.30 (t, J=7.0 Hz, 3H), 1.20 (t, J=7.1 Hz, 3H).

The following compounds were prepared in like manner to the procedureoutlined in Example 98:

1,2-Dichloro-4-(trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzene(C444)

Isolated as a brown oil (184 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.43 (d,J=8.2 Hz, 1H), 7.36 (dd, J=2.2, 0.7 Hz, 1H), 7.10 (ddd, J=8.3, 2.1, 0.7Hz, 1H), 4.59 (d, J=6.2 Hz, 1H), 3.82-3.55 (m, 4H), 2.77 (d, J=8.5 Hz,1H), 2.24 (dd, J=8.5, 6.3 Hz, 1H), 1.30 (t, J=7.0 Hz, 3H), 1.20 (t,J=7.1 Hz, 3H).

1,2,3-Trichloro-5-(trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzene(C445)

Isolated as a brown oil (146 g, 93%): ¹H NMR (400 MHz, CDCl₃) δ 7.29 (d,J=0.7 Hz, 2H), 4.59 (d, J=6.1 Hz, 1H), 3.82-3.54 (m, 4H), 2.75 (d, J=8.5Hz, 1H), 2.23 (dd, J=8.5, 6.1 Hz, 1H), 1.30 (t, J=7.0 Hz, 3H), 1.20 (t,J=7.0 Hz, 3H).

trans-1,3-Dichloro-5-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-2-methoxybenzene(C446)

Isolated as an orange oil (2.254 g, 80%): ¹H NMR (400 MHz, CDCl₃) δ 7.20(d, J=0.5 Hz, 2H), 4.58 (d, J=6.2 Hz, 1H), 3.90 (s, 3H), 3.67 (m, 4H),2.74 (d, J=8.5 Hz, 1H), 2.22 (dd, J=8.5, 6.2 Hz, 1H), 1.31 (m, 3H), 1.21(m, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 151.87, 131.55, 129.27, 129.20,127.21, 101.21, 62.39, 61.88, 61.68, 60.70, 37.67, 36.96, 15.34, 15.25;EIMS m/z 387.

2-Chloro-4-(trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-1-fluorobenzene(C447)

Isolated as a brown oil (63 g, 96%): ¹H NMR (400 MHz, CDCl₃) δ 7.44 (dd,J=7.0, 2.2 Hz, 1H), 7.29-7.22 (m, 1H), 7.09 (t, J=8.7 Hz, 1H), 6.62 (dd,J=16.1, 1.2 Hz, 1H), 6.14 (dd, J=16.1, 5.0 Hz, 1H), 5.05 (dd, J=4.9, 1.2Hz, 1H), 3.70 (dq, J=9.3, 7.0 Hz, 2H), 3.56 (dq, J=9.4, 7.1 Hz, 2H),1.25 (t, J=7.1 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃) δ 158.91, 156.42,133.65, 133.62, 130.47, 128.65, 128.07, 128.05, 126.39, 126.32, 121.26,121.08, 116.72, 116.51, 100.93, 61.17, 15.24; ¹⁹F NMR (376 MHz, CDCl₃) δ−116.36.

In another preparation, isolated as an amber oil (22.38 g, 88%): ¹H NMR(400 MHz, CDCl₃) δ 7.31 (m, 1H), 7.13 (m, 2H), 4.59 (d, J=6.3 Hz, 1H),3.69 (m, 4H), 2.78 (d, J=8.5 Hz, 1H), 2.23 (dd, J=8.5, 6.3 Hz, 1H), 1.30(t, J=7.1 Hz, 3H), 1.20 (t, J=7.1 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ−116.48; EIMS m/z 295 [M-OEt].

3-Chloro-5-(trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzonitrile(C448)

Isolated as yellow oil (4.8 g, 74%): ¹H NMR (400 MHz, CDCl₃) δ 7.59 (t,J=1.7 Hz, 1H), 7.50 (t, J=1.9 Hz, 1H), 7.45 (t, J=1.5 Hz, 1H), 4.61 (d,J=6.0 Hz, 1H), 3.89-3.50 (m, 4H), 2.83 (d, J=8.5 Hz, 1H), 2.28 (dd,J=8.4, 6.0 Hz, 1H), 1.31 (t, J=7.1 Hz, 3H), 1.21 (t, J=7.0 Hz, 3H).

Example 99: Preparation of(E)-1,3-dichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene (C449)

Step 1a: Acetaldehyde (120 g, 2688 mmol) was added to a stirred mixtureof 3,5-dichlorobenzaldehyde (96 g, 538 mmol) in toluene (400 mL) at 0°C. A solution of potassium hydroxide (3.35 g, 53.8 mmol) in methylalcohol (10 mL) was added dropwise via addition funnel. The resultingmixture was stirred at 0° C. for 4 hours until all of the3,5-dichlorobenzaldehyde was consumed by thin layer chromatography. Step1b: Ethyl acetate (500 mL) and concentrated hydrochloric acid (37%aqueous, 44.1 mL, 538 mmol) were added to the reaction mixture. Theresulting mixture was heated at 80° C., and a colorless liquid wasallowed to distill (200 mL). The reaction mixture was diluted with water(500 mL) and extracted with ethyl acetate. The organic layer was washedwith brine, dried over sodium sulfate, filtered, and concentrated toafford (E)-3-(3,5-dichlorophenyl) acrylaldehyde as a light yellow solid(115 g) which was used directly without further purification: ¹H NMR(300 MHz, CDCl₃) δ 9.72 (dd, J=7.4, 0.5 Hz, 1H), 7.43 (q, J=1.8 Hz, 3H),7.35 (d, J=16.0 Hz, 1H), 6.69 (dd, J=16.0, 7.4 Hz, 1H).

Step 2: Triethoxymethane (31.4 g, 208 mmol) and pyridin-1-ium4-methylbenzenesulfonate (0.528 g, 2.079 mmol) were added to a stirredsolution of (E)-3-(3,5-dichlorophenyl) acrylaldehyde (44 g, 208 mmol) inethanol (416 mL). The resulting mixture was stirred at 20° C. for 20hours. A solution of saturated aqueous sodium carbonate (50 mL) wasadded to the reaction mixture. The resulting mixture was concentrated at45° C. to remove the ethanol. The concentrate was diluted with water andextracted with hexane. The organic layer was washed with brine, driedover sodium sulfate, filtered and concentrated to afford the titleproduct as a light yellow oil (56.13 g, 93%): ¹H NMR (400 MHz, CDCl₃) δ7.25 (dt, J=10.6, 1.9 Hz, 3H), 6.61 (dd, J=16.1, 1.1 Hz, 1H), 6.22 (dd,J=16.1, 4.7 Hz, 1H), 5.17 (s, 1H), 5.14-5.00 (m, 1H), 3.78-3.49 (m, 4H),1.24 (q, J=7.2 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃) δ 139.34, 135.14,130.27, 129.88, 127.71, 125.08, 100.60, 61.20, 15.25.

The following compounds were prepared in like manner to the procedureoutlined in Example 99:

(E)-1,2-Dichloro-4-(3,3-diethoxyprop-1-en-1-yl)benzene (C450)

Isolated as an orange oil (142 g, 91%): ¹H NMR (300 MHz, CDCl₃) δ 7.48(d, J=2.0 Hz, 1H), 7.39 (dd, J=8.3, 0.8 Hz, 1H), 6.62 (d, J=16.1 Hz,1H), 6.20 (ddd, J=16.1, 4.9, 0.8 Hz, 1H), 5.06 (dt, J=4.9, 1.0 Hz, 1H),3.78-3.48 (m, 4H), 1.25 (td, J=7.1, 0.8 Hz, 6H).

(E)-1,2,3-Trichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene (C451)

Isolated as an orange oil (40 g, 91%): ¹H NMR (400 MHz, CDCl₃) δ 7.41(s, 2H), 6.58 (dd, J=16.1, 1.2 Hz, 1H), 6.21 (dd, J=16.1, 4.6 Hz, 1H),5.06 (dd, J=4.7, 1.2 Hz, 1H), 3.69 (dq, J=9.3, 7.1 Hz, 2H), 3.55 (dq,J=9.5, 7.0 Hz, 2H), 1.25 (t, J=7.1 Hz, 6H).

(E)-1,3-Dichloro-5-(3,3-diethoxyprop-1-en-1-yl)-2-methoxybenzene (C452)

Isolated as a yellow oil (2.305 g, 56%): ¹H NMR (400 MHz, CDCl₃) δ 7.32(s, 2H), 6.56 (d, J=16.0 Hz, 1H), 6.14 (dd, J=16.1, 4.8 Hz, 1H), 5.05(dd, J=4.8, 1.0 Hz, 1H), 3.89 (s, 3H), 3.69 (m, 2H), 3.55 (m, 2H), 1.25(t, J=7.1 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃) δ 151.75, 133.87, 129.87,129.45, 128.85, 126.91, 100.68, 61.14, 60.73, 15.24; EIMS m/z 304.

(E)-2-Chloro-4-(3,3-diethoxyprop-1-en-1-yl)-1-fluorobenzene (C453)

Isolated as an orange oil (283 g, 84%): ¹H NMR (400 MHz, CDCl₃) δ 7.44(dd, J=7.0, 2.2 Hz, 1H), 7.29-7.22 (m, 1H), 7.09 (t, J=8.7 Hz, 1H), 6.62(dd, J=16.1, 1.2 Hz, 1H), 6.14 (dd, J=16.1, 5.0 Hz, 1H), 5.05 (dd,J=4.9, 1.2 Hz, 1H), 3.70 (dq, J=9.3, 7.0 Hz, 2H), 3.56 (dq, J=9.4, 7.1Hz, 2H), 1.25 (t, J=7.1 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃) δ 158.91,156.42, 133.65, 133.62, 130.47, 128.65, 128.07, 128.05, 126.39, 126.32,121.26, 121.08, 116.72, 116.51, 100.93, 61.17, 15.24; ¹⁹F NMR (376 MHz,CDCl₃) δ −116.36.

In another preparation, isolated as a colorless oil (16.75 g, 64%): ¹HNMR (400 MHz, CDCl₃) δ 7.43 (dd, J=7.0, 2.2 Hz, 1H), 7.25 (m, 1H), 7.07(t, J=8.7 Hz, 1H), 6.62 (d, J=16.1 Hz, 1H), 6.13 (dd, J=16.1, 4.9 Hz,1H), 5.05 (dd, J=4.9, 1.0 Hz, 1H), 3.70 (dq, J=9.4, 7.1 Hz, 2H), 3.56(dq, J=9.4, 7.0 Hz, 2H), 1.25 (t, J=7.1 Hz, 6H); ¹³C NMR (101 MHz,CDCl₃) δ 158.91, 156.42, 133.65, 133.62, 130.47, 128.65, 128.07, 128.05,126.39, 126.32, 121.26, 121.08, 116.72, 116.51, 100.93, 61.17, 15.24;¹⁹F NMR (376 MHz, CDCl₃) δ −116.36; EIMS m/z 258.

(E)-3-Chloro-5-(3,3-diethoxyprop-1-en-1-yl)benzonitrile (C454)

Isolated as colorless oil (7.62 g, 62%): ¹H NMR (400 MHz, CDCl₃) δ 7.61(t, J=1.8 Hz, 1H), 7.58-7.53 (m, 1H), 7.51 (t, J=1.7 Hz, 1H), 6.72-6.61(m, 1H), 6.28 (dd, J=16.1, 4.5 Hz, 1H), 5.09 (dd, J=4.5, 1.3 Hz, 1H),3.70 (dq, J=9.4, 7.1 Hz, 2H), 3.56 (dq, J=9.4, 7.0 Hz, 2H), 1.26 (t,J=7.0 Hz, 6H).

Example 100: Preparation of(1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)-cyclopropane-1-carboxylicacid (C455)

1^(st) resolution: (R)-1-Phenylethanamine (6.49 g, 53.0 mmol) was slowlyadded to a stirred solution ofrac-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-carboxylic acid)(32.45 g, 106 mmol) in acetone (106 mL). The resulting solution wasstirred at 45° C. After a solid began to deposit, the mixture was placedat 5° C. for 4 hours. The solid was collected, washed with minimal coldacetone and dried. The white solid salt was diluted with ethyl acetate(100 mL) and washed with aqueous hydrochloric acid (1 N, 10 mL) andbrine (30 mL). The organic layer was dried over sodium sulfate, filteredand concentrated to afford the title product as a white solid (10.33 g,88% enantiomeric excess “ee”).

2^(nd) resolution: (R)-1-Phenylethanamine (3.4 g, 28 mmol) was slowlyadded to a stirred solution ofrac-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-carboxylic acid)(10.33 g, 88% ee) in acetone (100 mL). After 2 hours, a solid wascollected, washed with minimal cold acetone and dried. The solid wastreated with aqueous hydrochloric acid to afford the title compound as awhite solid (7.84 g, 97% ee, 24.2%): Specific Rotation: +47.4 (10 mg/mLin acetonitrile, 589 nm, 25.2° C.); ¹H NMR (300 MHz, CDCl₃) δ 7.36 (t,J=1.9 Hz, 1H), 7.17 (dd, J=1.9, 0.7 Hz, 2H), 3.48-3.37 (m, 1H), 2.87 (d,J=8.3 Hz, 1H); ¹³C NMR (400 MHz, DMSO-d₆) δ 166.28, 136.40, 133.39,127.27, 127.04, 61.36, 37.10, 35.98; ESIMS m/z 298.9 ([M−H]⁻).

ee was determined by Chiral HPLC method as follows: Column:CHIRALPAK^(@) ZWIX(+), particle size 3 μm, dimension 3 mm×150 mm, DAIC511584; Mobile phase: 49% acetonitrile/49% methanol/water with 50 mMformic acid and diethylamine; Flow rate: 0.5 mL/min; Time: 9 min;Temperature: 25° C.

The following compounds were prepared in like manner to the procedureoutlined in Example 100:

(1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxylicacid (C456)

Isolated as a white solid (6.7 g, 30%, 96% ee). Analytical data areconsistent with racemic acid C3.

(1R,3R)-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylicacid (C457)

Isolated as a white solid (0.5 g, 13%, 99% ee). Analytical data areconsistent with racemic acid C16.

(1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxylicacid (C458)

Isolated as a white solid (2 g, 29%, 99% ee). Analytical data areconsistent with racemic acid C2.

Example 101: Preparation of(1S,3S)-2,2-Dichloro-3-(3,5-dichlorophenyl)-cyclopropane-1-carboxylicacid (C459)

The mother liquor from the 1^(st) R,R-acid resolution (from Example 100)was concentrated and dissolved in acetone (˜100 mL) and warmed to 45° C.With swirling, (S)-1-phenylethanamine (5.0 g, 41.2 mmol, 0.8 eq.) wasadded. The resulting solution was stirred at 45° C. After a solid beganto deposit, the mixture was placed at 5° C. for 2 hours. A solid wascollected, washed with minimal cold acetone and vacuum-dried at 35° C.The solid was treated with aqueous hydrochloric acid to provide the freeS,S-acid as a white solid (9.87 g, 85% ee, 59% yield). A secondresolution of the 85% ee combined S,S-acid (13.45 g, 41.7 mmol, 85% ee)using the same procedure with (S)-1-phenylethanamine (3.8 g, 31.3 mmol,0.75 eq.) provided the S,S-acid as a white solid (8.53 g, 26%, 99% ee).Specific Rotation: −51.9 (10 mg/mL in acetonitrile, 589 nm, 25.2° C.).Analytical data are consistent with racemic acid C1.

ee was determined by Chiral HPLC method as follows: Column:CHIRALPAK^(@) ZWIX(+), particle size 3 μm, dimension 3 mm×150 mm L, DAIC511584; Mobile phase: 49% acetonitrile/49% methanol/water with 50 mMformic acid and diethylamine; Flow rate: 0.5 mL/min; Time: 9 min;Temperature: 25° C.

The following compounds were prepared in like manner to the procedureoutlined in Example 101:

(1S,3S)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxylicacid (C460)

Isolated as a white solid (7 g, 35%, 98% ee). Analytical data areconsistent with racemic acid C3.

(1S,3S)-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylicacid (C461)

Isolated as a white solid (0.64 g, 27%, 98% ee). Analytical data areconsistent with racemic acid C16.

(1S,3S)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxylicacid

Isolated as a white solid (0.75 g, 41%, 99% ee). Analytical data areconsistent with racemic acid C2.

The following compounds were prepared in like manner to the procedureoutlined in Example 1:

trans-2,2-dichloro-3-(perfluorophenyl)cyclopropane-1-carboxylic acid(C463)

Isolated as a white solid (1.44 g, 67%): ¹H NMR (400 MHz, CDCl₃) δ 10.19(s, 1H), 3.30 (d, J=8.2 Hz, 1H), 3.09 (d, J=8.3 Hz, 1H); ¹⁹F NMR (376MHz, CDCl₃) δ −140.52, −140.54, −140.58, −140.60, −152.14, −152.20,−152.25, −160.82, −160.84, −160.87, −160.89, −160.93, −160.95; ESIMS m/z320 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 4:

trans-1-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-2,3,4,5,6-pentafluorobenzene(C464)

Isolated as a gold oil (1.38 g, 77%): ¹H NMR (400 MHz, Chloroform-d) δ7.32-7.22 (m, 2H), 6.99-6.89 (m, 2H), 3.83 (s, 3H), 3.30 (d, J=8.8 Hz,1H), 2.89 (d, J=8.8 Hz, 1H). ¹⁹F NMR (376 MHz, CDCl₃) δ −140.30,−140.34, −153.63, −153.74, −61.68, −161.70, −161.73.

EIMS m/z 383.

Example 102: Preparation of(E/Z)-1,2,3,4,5-pentafluoro-6-(4-methoxystyryl)benzene (C465)

n-Butyl lithium solution (2.5 M in hexane, 4.1 mL, 10.2 mmol) was addeddropwise to a stirred solution of (4-methoxybenzyl)triphenylphosphoniumchloride (4.27 g, 10.2 mmol), in dry tetrahydrofuran (50 mL) at −30° C.The resulting reddish slurry was stirred at −25 to −30° C. for 30minutes. 2,3,4,5,6-Pentafluorobenzaldehyde (2.0 g, 10.2 mmol) in drytetrahydrofuran (5 mL) was added dropwise, and the resulting whiteslurry was stirred at −30° C. for 2 hours and at room temperatureovernight. The reaction mixture was carefully quenched with water (˜100mL), and the aqueous mixture was extracted with ethyl ether (3×50 mL).The combined organic extracts were washed with water and brine, driedover anhydrous magnesium sulfate, filtered, and concentrated underreduced pressure on a rotary evaporator. Purification of the crudemixture by silica gel flash chromatography with a mobile phase of 100%hexanes to 25% ethyl acetate in hexanes gaveE/Z-1,2,3,4,5-pentafluoro-6-(4-methoxystyryl)benzene (about an 8:2mixture of E- and Z-isomers) as a white solid (1.7 g, 52.7%): ¹H NMR(400 MHz, CDCl₃) δ 7.53-7.43 (m, 2H), 7.38 (d, J=16.7 Hz, 1H), 7.00-6.74(m, 3H), 3.82 (d, J=21.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 160.38,136.73, 129.32, 129.27, 128.28, 114.30, 113.92, 112.78, 110.43, 110.40,77.32, 77.20, 77.00, 76.68, 55.36, 55.20; EIMS m/z 300.

Example 103: Preparation ofcis-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxylic acid(C466)

Sodium chloride (1.0 g, 11.06 mmol) was added portionwise to a stirredsolution ofcis-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde(C467) (0.897 g, 3.16 mmol), sodium dihydrogenphosphate (0.758 g, 6.32mmol), 2-methylbut-2-ene (2.0 M solution in tetrahydrofuran, 7.1 mL,14.21 mmol) in acetone (12 mL) and water (4 mL). The resulting paleyellow solution was stirred at room temperature for 4 hours, then pouredinto water (100 mL) and acidified to pH=2 with aqueous hydrochloric acid(1 N). The aqueous mixture was extracted with ethyl acetate (3×50 mL).The combined organic extracts were washed with water and brine, driedover anhydrous magnesium sulfate, filtered, and concentrated underreduced pressure on a rotary evaporator. Purification by C-18 flashchromatography (to remove the trans isomer byproduct) gavecis-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylic acid asa white solid (0.225 g, 22.6%): ¹H NMR (400 MHz, CDCl₃) δ 8.04 (s, 1H),7.32 (td, J=1.9, 0.8 Hz, 1H), 7.21 (dd, J=1.9, 1.0 Hz, 2H), 3.28 (dt,J=11.2, 1.0 Hz, 1H), 2.93 (d, J=11.1 Hz, 1H).

Example 104: Preparation ofcis-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde(C467)

p-Toluenesulfonic acid monohydrate (2.19 g, 11.52 mmol) was added to astirred solution of2-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropyl)-1,3-dioxolane(C468) (0.945 g, 2.88 mmol), in 1:1 tetrahydrofuran/water (20 mL). Thesolution was heated at 70° C. for a total of 36 hours, cooled, andpoured into water (200 mL). The aqueous mixture was extracted with ethylacetate (3×50 mL). The combined organic extracts were washed with waterand brine, dried over anhydrous magnesium sulfate, filtered, andconcentrated under reduced pressure on a rotary evaporator. Purificationby silica gel flash chromatography yieldedcis-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde as ayellow oil (0.897 g, 93%): EIMS m/z 284.

Example 105: Preparation of2-(cis-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropyl)-1,3-dioxolane(C468)

Powdered sodium hydroxide (8.16 g, 204 mmol) was added portionwise to astirred solution of (Z)-2-(3,5-dichlorostyryl)-1,3-dioxolane (C469) (5g, 20.4 mmol), and tetrabutylammonium hexafluorophosphate(V) (0.395 g,1.02 mmol) in chloroform (32.7 mL) and water (0.294 mL). Theheterogeneous mixture was stirred at 35° C. for 12 hours and then waspoured into water (100 mL). The aqueous mixture was extracted with ethylacetate (3×100 mL). The combined organic extracts were washed with waterand brine, dried over anhydrous magnesium sulfate, filtered, andconcentrated under reduced pressure on a rotary evaporator. Purificationby silica gel flash chromatography with a mobile phase of ethyl acetateand hexanes afforded2-(cis-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropyl)-1,3-dioxolane asa clear colorless oil (4.4 g, 62%): ¹H NMR (400 MHz, CDCl₃) δ 7.41 (dd,J=2.0, 1.1 Hz, 2H), 7.36-7.25 (m, 2H), 4.57 (d, J=8.0 Hz, 1H), 4.22-4.03(m, 2H), 4.04-3.85 (m, 2H), 3.00 (dt, J=11.2, 1.1 Hz, 1H), 2.19 (dd,J=11.1, 8.0 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 135.17, 134.94, 128.95,128.08, 127.28, 102.06, 77.32, 77.20, 77.00, 76.68, 65.39, 65.28, 59.78,36.38, 35.96; EIMS m/z 328.

Example 106: Preparation of (Z)-2-(3,5-dichlorostyryl)-1,3-dioxolane(C469)

Tris(dioxa-3,6-heptyl)amine (27.7 g, 86.0 mmol) was added dropwise to astirred solution of 3,5-dichlorobenzaldehyde (15 g, 86 mmol), and((1,3-dioxolan-2-yl)methyl)triphenylphosphonium bromide (36.8 g, 86mmol) in 1:1 dichloromethane/water (400 mL). To the biphasic mixture wasthen added potassium carbonate (11.85 g, 86 mmol). The reaction mixturewas heated at reflux for a total of 20 hours, cooled, and poured intowater (200 mL). The aqueous mixture was extracted with dichloromethane(3×100 mL). The combined organic extracts were washed with water andbrine, dried over anhydrous magnesium sulfate, filtered, andconcentrated under reduced pressure on a rotary evaporator. Purificationby silica gel flash chromatography with a mobile phase of ethyl acetateand hexanes gave (Z)-2-(3,5-dichlorostyryl)-1,3-dioxolane as a waxywhite solid (11.2 g, 53%): ¹H NMR (400 MHz, CDCl₃) δ 7.37-7.18 (m, 3H),6.65 (d, J=11.7 Hz, 1H), 5.80 (dd, J=11.8, 7.4 Hz, 1H), 5.43 (dd, J=7.4,0.9 Hz, 1H), 4.18-4.02 (m, 2H), 4.03-3.87 (m, 2H); EIMS m/z 245.

Example 107: Preparation oftrans-2-bromo-2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylicacid (C470)

Powdered sodium hydroxide (0.727 g, 18.17 mmol) was added portionwise toa stirring solution of(E)-1,3-dichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene (C449) (0.5 g,1.82 mmol) and tetrabutylammonium hexafluorophosphate (0.07 g, 0.182mmol) dibromochloromethane (5 mL). The resulting yellow suspension ofsolids was heated to 45° C. for a total of 7 hours, cooled, and quenchedwith water (100 mL). The mixture was extracted with ether (3×50 mL). Thecombined organic extracts were washed with water and brine, dried overanhydrous magnesium sulfate, filtered, and concentrated under reducedpressure on a rotary evaporator. Purification by silica gel flashchromatography with a mobile phase of ethyl acetate and hexanes gavetrans-1-(2-bromo-2-chloro-3-(diethoxymethyl)cyclopropyl)-3,5-dichlorobenzene(0.38 g, 34.2%) as a yellow oil.

Aqueous hydrochloric acid (2 N, 5 mL, 10 mmol) was added dropwise to astirring solution oftrans-1-(2-bromo-2-chloro-3-(diethoxymethyl)cyclopropyl)-3,5-dichlorobenzene(0.38 g, 0.956 mmol) in acetone (10 mL). The resulting colorlesssolution was heated at 35° C. for a total of 8 hours, cooled, and pouredinto water (100 mL). The aqueous mixture was extracted with ethylacetate (3×50 mL). The combined organic extracts were washed with waterand brine, dried over anhydrous magnesium sulfate, filtered, andconcentrated under reduced pressure on a rotary evaporator. Purificationby silica gel flash chromatography with a mobile phase of ethyl acetateand hexanes affordedtrans-2-bromo-2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde(120 mg, 36.3%) as a yellow oil.

2-Methylbutene (2.0 M in tetrahydrofuran, 0.82 mL, 1.644 mmol) was addeddropwise to a stirring solution oftrans-2-bromo-2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde(120 mg, 0.365 mmol) and sodium dihydrogenphosphate (88 mg, 0.731 mmol)in acetone (3 mL) and water (1 mL). The resulting colorless cloudysuspension was treated with 80% sodium chlorite (147 mg, 1.297 mmol).The reaction mixture was stirred at room temperature for 12 hours,quenched with aqueous hydrochloric acid (1 N, 10 mL), and extracted withethyl acetate (3×50 mL). The combined organic extracts were washed withwater and brine, dried over anhydrous magnesium sulfate, filtered, andconcentrated under reduced pressure on a rotary evaporator. Purificationby C-18 flash chromatography (acetonitrile/water) providedtrans-2-bromo-2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxylicacid as a white solid (0.083 g, 62.7%): ¹H NMR (400 MHz, CDCl₃) δ 7.37(q, J=1.8 Hz, 2H), 7.17 (ddd, J=7.0, 1.9, 0.7 Hz, 1H), 3.39 (dd, J=56.9,8.2 Hz, 1H), 2.88 (dd, J=45.2, 8.3 Hz, 1H); ESIMS m/z 343 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 107:

trans-2-Bromo-3-(3,5-dichlorophenyl)-2-fluorocyclopropane-1-carboxylicacid (C471)

Isolated as a white solid (0.098 g, 51.2%): ¹H NMR (400 MHz, CDCl₃) δ8.31 (s, 1H), 7.35 (dt, J=6.0, 1.9 Hz, 1H), 7.15 (dd, J=15.6, 1.8 Hz,2H), 3.61-3.18 (m, 1H), 2.95-2.68 (m, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−134.90, −135.76, −135.78; ESIMS m/z 327 ([M−H]⁻).

trans-2-Chloro-3-(3,5-dichlorophenyl)-2-fluorocyclopropane-1-carboxylicacid (C472)

Isolated as a pale yellow solid (0.107 g, 46.1%): ¹H NMR (400 MHz,CDCl₃) δ 8.69 (s, 1H), 7.35 (dt, J=4.0, 1.9 Hz, 1H), 7.26-7.10 (m, 2H),3.77-3.12 (m, 1H), 3.07-2.63 (m, 1H); ESIMS m/z 282 ([M−H]⁻).

It is recognized that some reagents and reaction conditions may not becompatible with certain functionalities that may be present in certainmolecules of Formula One or certain molecules used in the preparation ofcertain molecules of Formula One. In such cases, it may be necessary toemploy standard protection and deprotection protocols comprehensivelyreported in the literature and well known to a person skilled in theart. In addition, in some cases it may be necessary to perform furtherroutine synthetic steps not described herein to complete the synthesisof desired molecules. A person skilled in the art will also recognizethat it may be possible to achieve the synthesis of desired molecules byperforming some of the steps of the synthetic routes in a differentorder to that described. A person skilled in the art will also recognizethat it may be possible to perform standard functional groupinterconversions or substitution reactions on desired molecules tointroduce or modify substituents.

Biological Assays

The following bioassays against Beet Armyworm (Spodoptera exigua),Cabbage Looper (Trichoplusia ni), Green Peach Aphid (Myzus persicae),and Yellow Fever Mosquito (Aedes aegypti), are included herein due tothe damage they inflict. Furthermore, the Beet Armyworm and CabbageLooper are two good indicator species for a broad range of chewingpests. Additionally, the Green Peach Aphid is a good indicator speciesfor a broad range of sap-feeding pests. The results with these threeindicator species along with the Yellow Fever Mosquito show the broadusefulness of the molecules of Formula One in controlling pests in PhylaArthropoda, Mollusca, and Nematoda (Drewes et al.)

Example A: Bioassays on Beet Armyworm (Spodoptera exigua, LAPHEG)(“BAW”), and Cabbage Looper (Trichoplusia ni, TRIPNI) (“CL”)

Beet armyworm is a serious pest of economic concern for alfalfa,asparagus, beets, citrus, corn, cotton, onions, peas, peppers, potatoes,soybeans, sugar beets, sunflowers, tobacco, and tomatoes, among othercrops. It is native to Southeast Asia but is now found in Africa,Australia, Japan, North America, and Southern Europe. The larvae mayfeed in large swarms causing devastating crop losses. It is known to beresistant to several pesticides.

Cabbage looper is a serious pest found throughout the world. It attacksalfalfa, beans, beets, broccoli, Brussel sprouts, cabbage, cantaloupe,cauliflower, celery, collards, cotton, cucumbers, eggplant, kale,lettuce, melons, mustard, parsley, peas, peppers, potatoes, soybeans,spinach, squash, tomatoes, turnips, and watermelons, among other crops.This species is very destructive to plants due to its voraciousappetite. The larvae consume three times their weight in food daily. Thefeeding sites are marked by large accumulations of sticky, wet, fecalmaterial, which may contribute to higher disease pressure therebycausing secondary problems on the plants in the site. It is known to beresistant to several pesticides.

Consequently, because of the above factors control of these pests isimportant. Furthermore, molecules that control these pests (BAW and CL),which are known as chewing pests, will be useful in controlling otherpests that chew on plants.

Certain molecules disclosed in this document were tested against BAW andCL using procedures described in the following examples. In thereporting of the results, the “BAW & CL Rating Table” was used (SeeTable Section).

Bioassays on BAW

Bioassays on BAW were conducted using a 128-well diet tray assay. One tofive second instar BAW larvae were placed in each well (3 mL) of thediet tray that had been previously filled with approximately 1.5 mL ofartificial diet to which 50 μg/cm² of the test molecule (dissolved in 50μL of 90:10 acetone-water mixture) had been applied (to each of eightwells) and then allowed to dry. Trays were covered with a clearself-adhesive cover, vented to allow gas exchange, and held at 25° C.,14:10 light-dark for five to seven days. Percent mortality was recordedfor the larvae in each well; activity in the eight wells was thenaveraged. The results are indicated in the table entitled “Table ABC:Biological Results” (See Table Section).

Bioassays on CL

Bioassays on CL were conducted using a 128-well diet tray assay. one tofive second instar CL larvae were placed in each well (3 mL) of the diettray that had been previously filled with 1 mL of artificial diet towhich 50 μg/cm² of the test molecule (dissolved in 50 μL of 90:10acetone-water mixture) had been applied (to each of eight wells) andthen allowed to dry. Trays were covered with a clear self-adhesivecover, vented to allow gas exchange, and held at 25° C., 14:10light-dark for five to seven days. Percent mortality was recorded forthe larvae in each well; activity in the eight wells was then averaged.The results are indicated in the table entitled “Table ABC: BiologicalResults” (See Table Section).

Example B: Bioassays on Green Peach Aphid (Myzus persicae, MYZUPE)(“GPA”)

GPA is the most significant aphid pest of peach trees, causing decreasedgrowth, shriveling of the leaves, and the death of various tissues. Itis also hazardous because it acts as a vector for the transport of plantviruses, such as potato virus Y and potato leafroll virus to members ofthe nightshade/potato family Solanaceae, and various mosaic viruses tomany other food crops. GPA attacks such plants as broccoli, burdock,cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce,macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, andzucchini, among other crops. GPA also attacks many ornamental crops suchas carnation, chrysanthemum, flowering white cabbage, poinsettia, androses. GPA has developed resistance to many pesticides. Currently, it isa pest that has the third largest number of reported cases of insectresistance (Sparks et al.). Consequently, because of the above factorscontrol of this pest is important. Furthermore, molecules that controlthis pest (GPA), which is known as a sap-feeding pest, are useful incontrolling other pests that feed on the sap from plants.

Certain molecules disclosed in this document were tested against GPAusing procedures described in the following example. In the reporting ofthe results, the “GPA & YFM Rating Table” was used (See Table Section).

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) trueleaves, were used as test substrate. The seedlings were infested with20-50 GPA (wingless adult and nymph stages) one day prior to chemicalapplication. Four pots with individual seedlings were used for eachtreatment. Test molecules (2 mg) were dissolved in 2 mL ofacetone/methanol (1:1) solvent, forming stock solutions of 1000 ppm testmolecule. The stock solutions were diluted 5× with 0.025% Tween 20 inwater to obtain the solution at 200 ppm test molecule. A hand-heldaspirator-type sprayer was used for spraying a solution to both sides ofcabbage leaves until runoff. Reference plants (solvent check) weresprayed with the diluent only containing 20% by volume ofacetone/methanol (1:1) solvent. Treated plants were held in a holdingroom for three days at approximately 25° C. and ambient relativehumidity (RH) prior to grading. Evaluation was conducted by counting thenumber of live aphids per plant under a microscope. Percent control wasmeasured using Abbott's correction formula (W. S. Abbott, “A Method ofComputing the Effectiveness of an Insecticide” J. Econ. Entomol. 18(1925), pp. 265-267) as follows. Corrected % Control=100*(X−Y)/X whereX=No. of live aphids on solvent check plants and Y=No. of live aphids ontreated plants. The results are indicated in the table entitled “TableABC: Biological Results” (See Table Section).

Example C: Bioassays on Yellow Fever Mosquito (Aedes aegypti, AEDSAE)(“YFM”)

YFM prefers to feed on humans during the daytime and is most frequentlyfound in or near human habitations. YFM is a vector for transmittingseveral diseases. It is a mosquito that can spread the dengue fever andyellow fever viruses. Yellow fever is the second most dangerousmosquito-borne disease after malaria. Yellow fever is an acute viralhemorrhagic disease and up to 50% of severely affected persons withouttreatment will die from yellow fever. There are an estimated 200,000cases of yellow fever, causing 30,000 deaths worldwide each year. Denguefever is a nasty, viral disease; it is sometimes called “breakbonefever” or “break-heart fever” because of the intense pain it canproduce. Dengue fever kills about 20,000 people annually. Consequently,because of the above factors control of this pest is important.Furthermore, molecules that control this pest (YFM), which is known as asucking pest, are useful in controlling other pests that cause human andanimal suffering.

Certain molecules disclosed in this document were tested against YFMusing procedures described in the following paragraph. In the reportingof the results, the “GPA & YFM Rating Table” was used (See TableSection).

Master plates containing 400 μg of a molecule dissolved in 100 μL ofdimethyl sulfoxide (DMSO) (equivalent to a 4000 ppm solution) are used.A master plate of assembled molecules contains 15 μL per well. To thisplate, 135 μL of a 90:10 water/acetone mixture is added to each well. Arobot is programmed to dispense 15 μL aspirations from the master plateinto an empty 96-well shallow plate (“daughter” plate). There are 6 reps(“daughter” plates) created per master. The created “daughter” platesare then immediately infested with YFM larvae.

The day before plates are to be treated, mosquito eggs are placed inMillipore water containing liver powder to begin hatching (4 g. into 400mL). After the “daughter” plates are created using the robot, they areinfested with 220 μL of the liver powder/larval mosquito mixture (about1 day-old larvae). After plates are infested with mosquito larvae, anon-evaporative lid is used to cover the plate to reduce drying. Platesare held at room temperature for 3 days prior to grading. After 3 days,each well is observed and scored based on mortality. The results areindicated in the table entitled “Table ABC: Biological Results” (SeeTable Section).

Agriculturally Acceptable Acid Addition Salts, Salt Derivatives,Solvates, Ester Derivatives, Polymorphs, Isotopes, and Radionuclides

Molecules of Formula One may be formulated into agriculturallyacceptable acid addition salts. By way of a non-limiting example, anamine function can form salts with hydrochloric, hydrobromic, sulfuric,phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric,oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic,aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic,hydroxyl-methanesulfonic, and hydroxyethanesulfonic acids. Additionally,by way of a non-limiting example, an acid function can form saltsincluding those derived from alkali or alkaline earth metals and thosederived from ammonia and amines. Examples of preferred cations includesodium, potassium, and magnesium.

Molecules of Formula One may be formulated into salt derivatives. By wayof a non-limiting example, a salt derivative may be prepared bycontacting a free base with a sufficient amount of the desired acid toproduce a salt. A free base may be regenerated by treating the salt witha suitable dilute aqueous base solution such as dilute aqueous sodiumhydroxide, potassium carbonate, ammonia, and sodium bicarbonate. As anexample, in many cases, a pesticide, such as 2,4-D, is made morewater-soluble by converting it to its dimethylamine salt.

Molecules of Formula One may be formulated into stable complexes with asolvent, such that the complex remains intact after the non-complexedsolvent is removed. These complexes are often referred to as “solvates.”However, it is particularly desirable to form stable hydrates with wateras the solvent.

Molecules of Formula One containing an acid functionality may be madeinto ester derivatives. These ester derivatives can then be applied inthe same manner as the molecules disclosed in this document are applied.

Molecules of Formula One may be made as various crystal polymorphs.Polymorphism is important in the development of agrochemicals sincedifferent crystal polymorphs or structures of the same molecule can havevastly different physical properties and biological performances.

Molecules of Formula One may be made with different isotopes. Ofparticular importance are molecules having ²H (also known as deuterium)or ³H (also known as tritium) in place of ¹H. Molecules of Formula Onemay be made with different radionuclides. Of particular importance aremolecules having ¹⁴C (also known as radiocarbon). Molecules of FormulaOne having deuterium, tritium, or ¹⁴C may be used in biological studiesallowing tracing in chemical and physiological processes and half-lifestudies, as well as, MoA studies.

Combinations

In another embodiment of this invention, molecules of Formula One may beused in combination (such as, in a compositional mixture, or asimultaneous or sequential application) with one or more activeingredients.

In another embodiment of this invention, molecules of Formula One may beused in combination (such as, in a compositional mixture, or asimultaneous or sequential application) with one or more activeingredients each having a MoA that is the same as, similar to, but morelikely—different from, the MoA of the molecules of Formula One.

In another embodiment, molecules of Formula One may be used incombination (such as, in a compositional mixture, or a simultaneous orsequential application) with one or more molecules having acaricidal,algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal,molluscicidal, nematicidal, rodenticidal, and/or virucidal properties.

In another embodiment, the molecules of Formula One may be used incombination (such as, in a compositional mixture, or a simultaneous orsequential application) with one or more molecules that areantifeedants, bird repellents, chemosterilants, herbicide safeners,insect attractants, insect repellents, mammal repellents, matingdisrupters, plant activators, plant growth regulators, and/orsynergists.

In another embodiment, molecules of Formula One may also be used incombination (such as in a compositional mixture, or a simultaneous orsequential application) with one or more biopesticides.

In another embodiment, in a pesticidal composition combinations of amolecule of Formula One and an active ingredient may be used in a widevariety of weight ratios. For example, in a two-component mixture, theweight ratio of a molecule of Formula One to an active ingredient, theweight ratios in Table B may be used. However, in general, weight ratiosless than about 10:1 to about 1:10 are preferred. It is also preferredsometimes to use a three, four, five, six, seven, or more, componentmixture comprising a molecule of Formula One and an additional two ormore active ingredients.

Weight ratios of a molecule of Formula One to an active ingredient mayalso be depicted as X:Y; wherein X is the parts by weight of a moleculeof Formula One and Y is the parts by weight of active ingredient. Thenumerical range of the parts by weight for X is 0<X≤100 and the parts byweight for Y is 0<Y≤100 and is shown graphically in TABLE C. By way ofnon-limiting example, the weight ratio of a molecule of Formula One toan active ingredient may be 20:1.

Ranges of weight ratios of a molecule of Formula One to an activeingredient may be depicted as X₁:Y₁ to X₂:Y₂, wherein X and Y aredefined as above.

In one embodiment, the range of weight ratios may be X₁:Y₁ to X₂:Y₂,wherein X₁>Y and X₂<Y₂. By way of non-limiting example, the range of aweight ratio of a molecule of Formula One to an active ingredient may bebetween 3:1 and 1:3, inclusive of the endpoints.

In another embodiment, the range of weight ratios may be X₁:Y₁ to X₂:Y₂,wherein X₁>Y₁ and X₂>Y₂. By way of non-limiting example, the range ofweight ratio of a molecule of Formula One to an active ingredient may bebetween 15:1 and 3:1, inclusive of the endpoints.

In another embodiment, the range of weight ratios may be X₁:Y₁ to X₂:Y₂,wherein X₁<Y and X₂<Y₂. By way of non-limiting example, the range ofweight ratios of a molecule of Formula One to an active ingredient maybe between about 1:3 and about 1:20, inclusive of the endpoints.

Formulations

A pesticide is many times not suitable for application in its pure form.It is usually necessary to add other substances so that the pesticidemay be used at the required concentration and in an appropriate form,permitting ease of application, handling, transportation, storage, andmaximum pesticide activity. Thus, pesticides are formulated into, forexample, baits, concentrated emulsions, dusts, emulsifiableconcentrates, fumigants, gels, granules, microencapsulations, seedtreatments, suspension concentrates, suspoemulsions, tablets, watersoluble liquids, water dispersible granules or dry flowables, wettablepowders, and ultra-low volume solutions.

Pesticides are applied most often as aqueous suspensions or emulsionsprepared from concentrated formulations of such pesticides. Suchwater-soluble, water-suspendable, or emulsifiable formulations areeither solids, usually known as wettable powders, water dispersiblegranules, liquids usually known as emulsifiable concentrates, or aqueoussuspensions. Wettable powders, which may be compacted to form waterdispersible granules, comprise an intimate mixture of the pesticide, acarrier, and surfactants. The concentration of the pesticide is usuallyfrom about 10% to about 90% by weight. The carrier is usually selectedfrom among the attapulgite clays, the montmorillonite clays, thediatomaceous earths, or the purified silicates. Effective surfactants,comprising from about 0.5% to about 10% of the wettable powder, arefound among sulfonated lignins, condensed naphthalenesulfonates,naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, andnon-ionic surfactants such as ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of pesticides comprise a convenientconcentration of a pesticide, such as from about 50 to about 500 gramsper liter of liquid dissolved in a carrier that is either a watermiscible solvent or a mixture of water-immiscible organic solvent andemulsifiers. Useful organic solvents include aromatics, especiallyxylenes and petroleum fractions, especially the high-boilingnaphthalenic and olefinic portions of petroleum such as heavy aromaticnaphtha. Other organic solvents may also be used, such as the terpenicsolvents including rosin derivatives, aliphatic ketones such ascyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitableemulsifiers for emulsifiable concentrates are selected from conventionalanionic and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticidesdispersed in an aqueous carrier at a concentration in the range fromabout 5% to about 50% by weight. Suspensions are prepared by finelygrinding the pesticide and vigorously mixing it into a carrier comprisedof water and surfactants. Ingredients, such as inorganic salts andsynthetic or natural gums may, also be added to increase the density andviscosity of the aqueous carrier. It is often most effective to grindand mix the pesticide at the same time by preparing the aqueous mixtureand homogenizing it in an implement such as a sand mill, ball mill, orpiston-type homogenizer. The pesticide in suspension might bemicroencapsulated in plastic polymer.

Oil dispersions (OD) comprise suspensions of organic solvent-insolublepesticides finely dispersed in a mixture of organic solvent andemulsifiers at a concentration in the range from about 2% to about 50%by weight. One or more pesticide might be dissolved in the organicsolvent. Useful organic solvents include aromatics, especially xylenesand petroleum fractions, especially the high-boiling naphthalenic andolefinic portions of petroleum such as heavy aromatic naphtha. Othersolvents may include vegetable oils, seed oils, and esters of vegetableand seed oils. Suitable emulsifiers for oil dispersions are selectedfrom conventional anionic and non-ionic surfactants. Thickeners orgelling agents are added in the formulation of oil dispersions to modifythe rheology or flow properties of the liquid and to prevent separationand settling of the dispersed particles or droplets.

Pesticides may also be applied as granular compositions that areparticularly useful for applications to the soil. Granular compositionsusually contain from about 0.5% to about 10% by weight of the pesticide,dispersed in a carrier that comprises clay or a similar substance. Suchcompositions are usually prepared by dissolving the pesticide in asuitable solvent and applying it to a granular carrier, which has beenpre-formed to the appropriate particle size, in the range of from about0.5 mm to about 3 mm. Such compositions may also be formulated by makinga dough or paste of the carrier and molecule, and then crushing anddrying to obtain the desired granular particle size. Another form ofgranules is a water emulsifiable granule (EG). It is a formulationconsisting of granules to be applied as a conventional oil-in-wateremulsion of the active ingredient(s), either solubilized or diluted inan organic solvent, after disintegration and dissolution in water. Wateremulsifiable granules comprise one or several active ingredient(s),either solubilized or diluted in a suitable organic solvent that is(are) absorbed in a water soluble polymeric shell or some other type ofsoluble or insoluble matrix.

Dusts containing a pesticide are prepared by intimately mixing thepesticide in powdered form with a suitable dusty agricultural carrier,such as kaolin clay, ground volcanic rock, and the like. Dusts cansuitably contain from about 1% to about 10% of the pesticide. Dusts maybe applied as a seed dressing or as a foliage application with a dustblower machine.

It is equally practical to apply a pesticide in the form of a solutionin an appropriate organic solvent, usually petroleum oil, such as thespray oils, which are widely used in agricultural chemistry.

Pesticides can also be applied in the form of an aerosol composition. Insuch compositions, the pesticide is dissolved or dispersed in a carrier,which is a pressure-generating propellant mixture. The aerosolcomposition is packaged in a container from which the mixture isdispensed through an atomizing valve.

Pesticide baits are formed when the pesticide is mixed with food or anattractant or both. When the pests eat the bait, they also consume thepesticide. Baits may take the form of granules, gels, flowable powders,liquids, or solids. Baits may be used in pest harborages.

Fumigants are pesticides that have a relatively high vapor pressure andhence can exist as a gas in sufficient concentrations to kill pests insoil or enclosed spaces. The toxicity of the fumigant is proportional toits concentration and the exposure time. They are characterized by agood capacity for diffusion and act by penetrating the pest'srespiratory system or being absorbed through the pest's cuticle.Fumigants are applied to control stored product pests under gas proofsheets, in gas sealed rooms or buildings, or in special chambers.

Pesticides may be microencapsulated by suspending the pesticideparticles or droplets in plastic polymers of various types. By altering,the chemistry of the polymer or by changing factors in the processing,microcapsules may be formed of various sizes, solubility, wallthicknesses, and degrees of penetrability. These factors govern thespeed with which the active ingredient within is released, which inturn, affects the residual performance, speed of action, and odor of theproduct. The microcapsules might be formulated as suspensionconcentrates or water dispersible granules.

Oil solution concentrates are made by dissolving pesticide in a solventthat will hold the pesticide in solution. Oil solutions of a pesticideusually provide faster knockdown and kill of pests than otherformulations due to the solvents themselves having pesticidal action andthe dissolution of the waxy covering of the integument increasing thespeed of uptake of the pesticide. Other advantages of oil solutionsinclude better storage stability, better penetration of crevices, andbetter adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, wherein the emulsioncomprises oily globules which are each provided with a lamellar liquidcrystal coating and are dispersed in an aqueous phase, wherein each oilyglobule comprises at least one molecule which is agriculturally active,and is individually coated with a monolamellar or oligolamellar layercomprising: (1) at least one non-ionic lipophilic surface-active agent,(2) at least one non-ionic hydrophilic surface-active agent, and (3) atleast one ionic surface-active agent, wherein the globules having a meanparticle diameter of less than 800 nanometers.

Other Formulation Components

Generally, when the molecules disclosed in Formula One are used in aformulation, such formulation can also contain other components. Thesecomponents include, but are not limited to, (this is a non-exhaustiveand non-mutually exclusive list) wetters, spreaders, stickers,penetrants, buffers, sequestering agents, drift reduction agents,compatibility agents, anti-foam agents, cleaning agents, andemulsifiers. A few components are described forthwith.

A wetting agent is a substance that when added to a liquid increases thespreading or penetration power of the liquid by reducing the interfacialtension between the liquid and the surface on which it is spreading.Wetting agents are used for two main functions in agrochemicalformulations: during processing and manufacture to increase the rate ofwetting of powders in water to make concentrates for soluble liquids orsuspension concentrates; and during mixing of a product with water in aspray tank to reduce the wetting time of wettable powders and to improvethe penetration of water into water-dispersible granules. Examples ofwetting agents used in wettable powder, suspension concentrate, andwater-dispersible granule formulations are: sodium lauryl sulfate;sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphaticalcohol ethoxylates.

A dispersing agent is a substance that adsorbs onto the surface ofparticles, helps to preserve the state of dispersion of the particles,and prevents them from reaggregating. Dispersing agents are added toagrochemical formulations to facilitate dispersion and suspension duringmanufacture, and to ensure the particles redisperse into water in aspray tank. They are widely used in wettable powders, suspensionconcentrates, and water-dispersible granules. Surfactants that are usedas dispersing agents have the ability to adsorb strongly onto a particlesurface and provide a charged or steric barrier to reaggregation ofparticles. The most commonly used surfactants are anionic, non-ionic, ormixtures of the two types. For wettable powder formulations, the mostcommon dispersing agents are sodium lignosulfonates. For suspensionconcentrates, very good adsorption and stabilization are obtained usingpolyelectrolytes, such assodium-naphthalene-sulfonate-formaldehyde-condensates. Tristyrylphenolethoxylate phosphate esters are also used. Non-ionics such asalkylarylethylene oxide condensates and EO-PO block copolymers aresometimes combined with anionics as dispersing agents for suspensionconcentrates. In recent years, new types of very high molecular weightpolymeric surfactants have been developed as dispersing agents. Thesehave very long hydrophobic ‘backbones’ and a large number of ethyleneoxide chains forming the ‘teeth’ of a ‘comb’ surfactant. These highmolecular weight polymers can give very good long-term stability tosuspension concentrates because the hydrophobic backbones have manyanchoring points onto the particle surfaces. Examples of dispersingagents used in agrochemical formulations are: sodium lignosulfonates;sodium naphthalene sulfonate formaldehyde condensates;tristyrylphenol-ethoxylate-phosphate-esters; aliphatic alcoholethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graftcopolymers.

An emulsifying agent is a substance that stabilizes a suspension ofdroplets of one liquid phase in another liquid phase. Without theemulsifying agent, the two liquids would separate into two immiscibleliquid phases. The most commonly used emulsifier blends contain analkylphenol or an aliphatic alcohol with twelve or more ethylene oxideunits and the oil-soluble calcium salt of dodecylbenzenesulfonic acid. Arange of hydrophile-lipophile balance (“HLB”) values from about 8 toabout 18 will normally provide good stable emulsions. Emulsion stabilitycan sometimes be improved by the addition of a small amount of an EO-POblock copolymer surfactant.

A solubilizing agent is a surfactant that will form micelles in water atconcentrations above the critical micelle concentration. The micellesare then able to dissolve or solubilize water-insoluble materials insidethe hydrophobic part of the micelle. The types of surfactants usuallyused for solubilization are non-ionics, sorbitan monooleates, sorbitanmonooleate ethoxylates, and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additivessuch as mineral or vegetable oils as adjuvants to spray-tank mixes toimprove the biological performance of the pesticide on the target. Thetypes of surfactants used for bioenhancement depend generally on thenature and mode of action of the pesticide. However, they are oftennon-ionics such as: alkyl ethoxylates; linear aliphatic alcoholethoxylates; and aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation is a material addedto the pesticide to give a product of the required strength. Carriersare usually materials with high absorptive capacities, while diluentsare usually materials with low absorptive capacities. Carriers anddiluents are used in the formulation of dusts, wettable powders,granules, and water-dispersible granules.

Organic solvents are used mainly in the formulation of emulsifiableconcentrates, oil-in-water emulsions, suspoemulsions, oil dispersions,and ultra-low volume formulations, and to a lesser extent, granularformulations. Sometimes mixtures of solvents are used. The first maingroups of solvents are aliphatic paraffinic oils such as kerosene orrefined paraffins. The second main group (and the most common) comprisesthe aromatic solvents such as xylene and higher molecular weightfractions of C9 and C10 aromatic solvents. Chlorinated hydrocarbons areuseful as cosolvents to prevent crystallization of pesticides when theformulation is emulsified into water. Alcohols are sometimes used ascosolvents to increase solvent power. Other solvents may includevegetable oils, seed oils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used mainly in the formulation ofsuspension concentrates, oil dispersions, emulsions and suspoemulsionsto modify the rheology or flow properties of the liquid and to preventseparation and settling of the dispersed particles or droplets.Thickening, gelling, and anti-settling agents generally fall into twocategories, namely water-insoluble particulates and water-solublepolymers. It is possible to produce suspension concentrate and oildispersion formulations using clays and silicas. Examples of these typesof materials, include, but are not limited to, montmorillonite,bentonite, magnesium aluminum silicate, and attapulgite. Water-solublepolysaccharides in water based suspension concentrates have been used asthickening-gelling agents for many years. The types of polysaccharidesmost commonly used are natural extracts of seeds and seaweeds or aresynthetic derivatives of cellulose. Examples of these types of materialsinclude, but are not limited to, guar gum; locust bean gum; carrageenam;alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC); andhydroxyethyl cellulose (HEC). Other types of anti-settling agents arebased on modified starches, polyacrylates, polyvinyl alcohol, andpolyethylene oxide. Another good anti-settling agent is xanthan gum.

Microorganisms can cause spoilage of formulated products. Therefore,preservation agents are used to eliminate or reduce their effect.Examples of such agents include, but are not limited to: propionic acidand its sodium salt; sorbic acid and its sodium or potassium salts;benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt;methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often causes water-based formulations tofoam during mixing operations in production and in application through aspray tank. In order to reduce the tendency to foam, anti-foam agentsare often added either during the production stage or before fillinginto bottles. Generally, there are two types of anti-foam agents, namelysilicones and non-silicones. Silicones are usually aqueous emulsions ofdimethyl polysiloxane, while the non-silicone anti-foam agents arewater-insoluble oils, such as octanol and nonanol, or silica. In bothcases, the function of the anti-foam agent is to displace the surfactantfrom the air-water interface.

“Green” agents (e.g., adjuvants, surfactants, solvents) can reduce theoverall environmental footprint of crop protection formulations. Greenagents are biodegradable and generally derived from natural and/orsustainable sources, e.g. plant and animal sources. Specific examplesare: vegetable oils, seed oils, and esters thereof, also alkoxylatedalkyl polyglucosides.

Applications

Molecules of Formula One may be applied to any locus. Particular loci toapply such molecules include loci where alfalfa, almonds, apples,barley, beans, canola, corn, cotton, crucifers, flowers, fodder species(Rye Grass, Sudan Grass, Tall Fescue, Kentucky Blue Grass, and Clover),fruits, lettuce, oats, oil seed crops, oranges, peanuts, pears, peppers,potatoes, rice, sorghum, soybeans, strawberries, sugarcane, sugarbeets,sunflowers, tobacco, tomatoes, wheat (for example, Hard Red WinterWheat, Soft Red Winter Wheat, White Winter Wheat, Hard Red Spring Wheat,and Durum Spring Wheat), and other valuable crops are growing or theseeds thereof are going to be planted.

Molecules of Formula One may also be applied where plants, such ascrops, are growing and where there are low levels (even no actualpresence) of pests that can commercially damage such plants. Applyingsuch molecules in such locus is to benefit the plants being grown insuch locus. Such benefits, may include, but are not limited to: helpingthe plant grow a better root system; helping the plant better withstandstressful growing conditions; improving the health of a plant; improvingthe yield of a plant (e.g. increased biomass and/or increased content ofvaluable ingredients); improving the vigor of a plant (e.g. improvedplant growth and/or greener leaves); improving the quality of a plant(e.g. improved content or composition of certain ingredients); andimproving the tolerance to abiotic and/or biotic stress of the plant.

Molecules of Formula One may be applied with ammonium sulfate whengrowing various plants as this may provide additional benefits.

Molecules of Formula One may be applied on, in, or around plantsgenetically modified to express specialized traits, such as Bacillusthuringiensis (for example, Cry1Ab, Cry1Ac, Cry1Fa, Cry1A.105, Cry2Ab,Vip3A, mCry3A, Cry3Ab, Cry3Bb, Cry34Ab1/Cry35Ab1), other insecticidaltoxins, or those expressing herbicide tolerance, or those with “stacked”foreign genes expressing insecticidal toxins, herbicide tolerance,nutrition-enhancement, or any other beneficial traits.

Molecules of Formula One may be applied to the foliar and/or fruitingportions of plants to control pests. Either such molecules will come indirect contact with the pest, or the pest will consume such moleculeswhen eating the plant or while extracting sap or other nutrients fromthe plant.

Molecules of Formula One may also be applied to the soil, and whenapplied in this manner, root and stem feeding pests may be controlled.The roots may absorb such molecules thereby taking it up into the foliarportions of the plant to control above ground chewing and sap feedingpests.

Systemic movement of pesticides in plants may be utilized to controlpests on one portion of the plant by applying (for example by spraying alocus) a molecule of Formula One to a different portion of the plant.For example, control of foliar-feeding insects may be achieved by dripirrigation or furrow application, by treating the soil with for examplepre- or post-planting soil drench, or by treating the seeds of a plantbefore planting.

Molecules of Formula One may be used with baits. Generally, with baits,the baits are placed in the ground where, for example, termites can comeinto contact with, and/or be attracted to, the bait. Baits can also beapplied to a surface of a building, (horizontal, vertical, or slantsurface) where, for example, ants, termites, cockroaches, and flies, cancome into contact with, and/or be attracted to, the bait.

Molecules of Formula One may be encapsulated inside, or placed on thesurface of a capsule. The size of the capsules can range from nanometersize (about 100-900 nanometers in diameter) to micrometer size (about10-900 microns in diameter).

Molecules of Formula One may be applied to eggs of pests. Because of theunique ability of the eggs of some pests to resist certain pesticides,repeated applications of such molecules may be desirable to controlnewly emerged larvae.

Molecules of Formula One may be applied as seed treatments. Seedtreatment may be applied to all types of seeds, including those fromwhich plants genetically modified to express specialized traits willgerminate. Representative examples include those expressing proteinstoxic to invertebrate pests, such as Bacillus thuringiensis or otherinsecticidal toxins, those expressing herbicide tolerance, such as“Roundup Ready” seed, or those with “stacked” foreign genes expressinginsecticidal toxins, herbicide tolerance, nutrition-enhancement, droughttolerance, or any other beneficial traits. Furthermore, such seedtreatments with molecules of Formula One may further enhance the abilityof a plant to withstand stressful growing conditions better. Thisresults in a healthier, more vigorous plant, which can lead to higheryields at harvest time. Generally, about 1 gram of such molecules toabout 500 grams per 100,000 seeds is expected to provide good benefits,amounts from about 10 grams to about 100 grams per 100,000 seeds isexpected to provide better benefits, and amounts from about 25 grams toabout 75 grams per 100,000 seeds is expected to provide even betterbenefits. Molecules of Formula One may be applied with one or moreactive ingredients in a soil amendment.

Molecules of Formula One may be used for controlling endoparasites andectoparasites in the veterinary medicine sector or in the field ofnon-human-animal keeping. Such molecules may be applied by oraladministration in the form of, for example, tablets, capsules, drinks,granules, by dermal application in the form of, for example, dipping,spraying, pouring on, spotting on, and dusting, and by parenteraladministration in the form of, for example, an injection.

Molecules of Formula One may also be employed advantageously inlivestock keeping, for example, cattle, chickens, geese, goats, pigs,sheep, and turkeys. They may also be employed advantageously in petssuch as, horses, dogs, and cats. Particular pests to control would beflies, fleas, and ticks that are bothersome to such animals. Suitableformulations are administered orally to the animals with the drinkingwater or feed. The dosages and formulations that are suitable depend onthe species.

Molecules of Formula One may also be used for controlling parasiticworms, especially of the intestine, in the animals listed above.

Molecules of Formula One may also be employed in therapeutic methods forhuman health care. Such methods include, but are limited to, oraladministration in the form of, for example, tablets, capsules, drinks,granules, and by dermal application.

Molecules of Formula One may also be applied to invasive pests. Pestsaround the world have been migrating to new environments (for such pest)and thereafter becoming a new invasive species in such new environment.Such molecules may also be used on such new invasive species to controlthem in such new environments.

Before a pesticide may be used or sold commercially, such pesticideundergoes lengthy evaluation processes by various governmentalauthorities (local, regional, state, national, and international).Voluminous data requirements are specified by regulatory authorities andmust be addressed through data generation and submission by the productregistrant or by a third party on the product registrant's behalf, oftenusing a computer with a connection to the World Wide Web. Thesegovernmental authorities then review such data and if a determination ofsafety is concluded, provide the potential user or seller with productregistration approval. Thereafter, in that locality where the productregistration is granted and supported, such user or seller may use orsell such pesticide.

Molecules according to Formula One may be tested to determine itsefficacy against pests. Furthermore, mode of action studies may beconducted to determine if said molecule has a different mode of actionthan other pesticides. Thereafter, such acquired data may bedisseminated, such as by the internet, to third parties.

The headings in this document are for convenience only and must not beused to interpret any portion hereof.

Tables

TABLE B Weight Ratios Molecule of the Formula One:active ingredient100:1 to 1:100 50:1 to 1:50 20:1 to 1:20 10:1 to 1:10 5:1 to 1:5 3:1 to1:3 2:1 to 1:2 1:1

TABLE C active ingredient (Y) 100 X_(,) Y X, Y X, Y Parts by weight  50X, Y X, Y X, Y X, Y X, Y  20 X, Y X, Y X, Y X, Y X, Y  15 X, Y X, Y X, YX, Y X, Y  10 X, Y X, Y   5 X, Y X, Y X, Y X, Y  3 X, Y X, Y X, Y X, YX, Y X, Y X, Y  2 X, Y X, Y X, Y X, Y X, Y  1 X, Y X, Y X, Y X, Y X, YX, Y X, Y X, Y X, Y 1 2 3 5 10 15 20 50 100 molecule of Formula One (X)Parts by weight

TABLE 2 Structure and preparation method for F Series molecules No.Structure Prep.* F1

13 F2

13 F3

13 F4

13 F5

13 F6

13 F7

13 F8

13 F9

13 F10

13 F11

13 F12

13 F13

13 F14

13 F15

13 F16

13 F17

13 F18

13 F19

13 F20

13 F21

13 F22

13 F23

13 F24

13 F25

13 F26

13 F27

13 F28

13 F29

13 F30

13 F31

13 F32

13 F33

13 F34

13 F35

13 F36

13 F37

13 F38

13 F39

13 F40

13 F41

13 F42

13 F43

13 F44

13 F45

13 F46

13 F47

13 F48

13 F49

13 F50

13 F51

13 F52

13 F53

13 F54

13 F55

13 F56

13 F57

13 F58

13 F59

13 F60

13 F61

13 F62

13 F63

13 F64

13 F65

13 F66

13 F67

13 F68

13 F69

13 F70

13 F71

13 F72

13 F73

13 F74

13 F75

13 F76

13 F77

13 F78

13 F79

13 F80

13 F81

13 F82

13 F83

13 F84

13 F85

13 F86

13 F87

13 F88

13 F89

13 F90

13 F91

13 F92

13 F93

13 F94

13 F95

13 F96

13 F97

13 F98

13 F99

13 F100

13 F101

13 F102

13 F103

13 F104

13 F105

13 F106

13 F107

13 F108

13 F109

13 F110

13 F111

13 F112

13 F113

13 F114

13 F115

13 F116

13 F117

13 F118

13 F119

13 F120

13 F121

13 F122

13 F123

13 F124

13 F125

13 F126

14 F127

14 F128

14 F129

14 F130

14 F131

14 F132

14 F133

14 F134

14 F135

14 F136

14 F137

15 F138

15 F139

16 F140

16 F141

16 F142

17 F143

17 F144

17 F145

17 F146

18 F147

18 F148

18 F149

18 F150

18 F151

18 F152

18 F153

18 F154

18 F155

18 F156

18 F157

19 F158

20 F159

20 F160

13 F161

13 F162

13 F163

13 F164

13 F165

14 F166

14 F167

15 F168

15 F169

14 F170

14 F171

18 F172

15 F173

15 F174

62 F175

62 F176

62 F177

62 F178

15 F179

56 F180

56 F181

56 F182

56 F183

13 F184

15 F185

14 F186

14 F187

15 F188

15 F189

15 F190

13 F191

13 F192

13 F193

13 F194

13 F195

62 F196

62 F197

15 F198

15 F199

62 F200

62 F201

62 F202

62 F203

13 F204

13 F205

62 F206

62 F207

62 F208

14 F209

14 F210

14 F211

14 F212

15 F213

15 F214

15 F215

15 F216

56 F217

13 F218

13 F219

13 F220

13 F221

13 F222

55 F223

62 F224

62 F225

62 F226

62 F227

62 F228

62 F229

54 F230

54 F231

54 F232

54 F233

54 F234

54 F235

54 F236

59 F237

65 F238

62 F239

62 F240

55 F241

55 F242

55 F243

13 F244

13 F245

62 F246

56 F247

56 F248

56 F249

56 F250

56 F251

55 F252

55 F253

55 F254

56 F255

56 F256

56 F257

55 F258

55 F259

56 F260

56 F261

56 F262

13 F263

13 F264

62 F265

62 F266

62 F267

57 F268

57 F269

55 F270

13 F271

13 F272

13 F273

13 F274

13 F275

55 F277

55 F278

55 F279

55 F280

55 F281

55 F282

55 F283

55 F284

55 F285

55 F286

55 F287

54 F288

70 F289

77 F290

55 F291

55 F292

55 F293

55 F294

55 F295

55 F296

55 F297

55 F298

54 F299

54 F300

54 F301

54 F302

54 F303

54 F304

54 F305

59 F306

13 F307

13 F308

13 F309

13 F310

13 F311

13 F312

55 F313

62 F314

62 F315

62 F316

13 F317

62 F318

55 F319

77 F320

13 F321

13 F322

13 F323

62 F324

62 F325

62 F326

62 F327

62 F328

62 F329

77 F330

13 F331

13 F332

13 F333

13 F334

13 F335

13 F336

62 F337

62 F338

62 F339

62 F340

13 F341

62 F342

13 F343

13 F344

62 F345

55 F346

55 F347

55 F348

55 F349

77 F350

77 F351

77 F352

77 F353

62 F354

62 F355

62 F356

62 F357

55 F358

55 F359

55 F360

62 F361

60 F362

59 F363

59 F364

55 F365

55 F366

55 F367

55 F368

55 F369

55 F370

55 F371

55 F372

55 F373

62 F374

55 F375

55 F376

55 F377

62 F378

62 F379

62 F380

62 F381

62 F382

77 F383

77 F384

77 F385

77 F386

77 F387

77 F388

55 F389

77 F390

77 F391

77 F392

77 F393

76 F394

76 F395

55 F396

55 F397

76 F398

76 F399

76 F400

76 F401

79 F402

62 F403

62 F404

62 F405

62 F406

62 F407

63 F408

62 F409

63 F410

79 F411

55 F412

55 F413

13 F414

13 F415

55 F416

55 F417

55 F418

55 F419

60 F420

63 F421

63 F422

13 F423

55 F424

55 F425

61 F426

62 F427

62 F428

62 F429

62 F430

62 F431

60 F432

60 F433

60 F434

15 F435

15 F436

15 F437

15 F438

15 F439

55 F440

13 F441

15 F442

15 F443

15 F444

15 F445

15 F446

13 F447

15 F448

15 F449

15 F450

15 F451

15 F452

15 F453

15 F454

15 F455

15 F456

15 F457

15 F458

55 F459

55 F460

55 F461

15 F462

55 F463

55 F464

55 F465

55 F468

55 F469

66 F470

55 F471

55 or 57 F472

55 F473

55 F474

55 F475

15 F476

55 F477

55 F478

55 F479

55 F480

73 F481

55 F482

15 F483

55 F484

55 F485

55 F486

55 F487

74 F488

55 F490

55 F491

55 F492

55 F493

15 F494

55 F495

72 F496

55 F497

55 F498

14 F499

13 F500

13 F501

13 F502

75 F503

13 F504

55 F505

55 F506

55 F507

55 F508

55 F509

55 F510

71 F511

55 F512

13 F513

13 F514

13 F515

13 F516

13 F517

55 F518

55 F519

55 F520

55 F521

55 F522

77 F523

77 F524

55 F525

59 F526

59 F527

55 F528

55 F529

55 F530

55 F531

55 F532

55 F533

55 F534

55 F535

55 F536

55 F537

55 F538

13 F539

13 F540

13 F541

13 F542

13 F543

13 F544

55 F545

55 F546

55 F547

55 F548

55 F549

55 F550

55 F551

55 F552

55 F553

55 F554

55 F555

55 F556

55 F557

55 F558

57 F559

57 F560

57 F561

57 F562

57 F563

57 F564

57 F565

57 F566

77 F567

55 F568

62 F569

62 F570

62 F571

62 F572

13 F573

13 F574

63 F575

60 F576

60 F577

60 F578

60 F579

62 F580

62 F581

55 F582

55 F583

55 F584

57 F585

57 F586

57 F587

57 F588

57 F589

57 F590

57 F591

57 F592

57 F593

57 F594

57 F595

57 F596

57 F597

57 F598

57 F599

57 F600

15 F601

15 F602

15 F603

15 F604

15 F605

15 F606

13 F607

13 F608

15 F609

15 F610

55 F611

55 F612

55 F613

55 F614

55 F615

55 F616

13 F617

13 F618

15 F619

15 F620

15 F621

62 F622

62 F623

62 F624

62 F625

62 F626

62 F627

62 F628

62 F629

14 PF1

13 PF2

13 PF4

13 PF5

13 PF6

56 PF7

13 PF8

13 PF9

13 PF10

18 PF11

18 PF12

18 PF13

18 PF14

18 PF15

18 PF16

18 PF17

80 PF18

80 PF19

80 PF20

80 PF21

64 PF22

62 PF24

69 PF25

67 PF26

67 PF27

67 PF28

67 PF29

69 PF30

67 PF31

67 PF32

13 PF33

13 PF34

13 PF35

13 PF36

57 PF37

13 PF38

13 PF39

13 PF40

13 PF41

13 PF42

13 PF43

18 PF44

18 PF45

18 PF46

13 PF47

13 PF48

13 PF49

13 PF50

13 PF51

13 PF52

15 PF53

15 PF54

15 PF55

15 PF56

17 PF57

17 PF58

15 PF59

17 PF60

17 PF61

17 PF62

17 PF65

13 PF66

13 PF67

13 PF68

13 PF69

58 PF70

14 PF71

14 PF72

13 PF73

17 PF74

17 PF75

17 PF76

18 PF77

55 PF78

55 PF102

17 PF104

67 PF107

67 PF108

68 PF109

68 PF110

15 PF113

14 PF114

14 PF115

14 PF116

14 PF117

14 PF118

14 PF119

13 PF120

14 PF122

14 PF123

14 PF124

14 PF125

14 PF126

14 PF127

14 PF130

17 PF133

55 PF134

13 PF135

55 PF136

15 PF138

13 PF139

13 PF140

13 PF141

13 PF143

55 PF148

13 PF152

15 PF153

13 PF155

13 PF156

56 PF158

13 PF161

68 PF162

68 PF163

67 PF164

68 *prepared according to example number

TABLE 3 Structure and preparation method for C series molecules No.Structure Prep* C1

1 C2

1 C3

1 C4

2 C5

2 C6

2 C7

2 C8

2 C9

2 C10

2 C11

2 C12

2 C13

2 C14

2 C15

2 C16

2 C17

2 C18

2 C19

2 C20

2 C21

2 C22

3 C23

3 C24

3 C25

4 C26

4 C27

4 C28

4 C29

4 C30

4 C31

4 C32

4 C33

4 C34

4 C35

4 C36

4 C37

4 C38

4 C39

4 C40

4 C41

4 C42

4 C43

5 C44

5 C45

5 C46

6 C47

6 C48

6 C49

6 C50

6 C51

6 C52

6 C53

6 C54

6 C55

6 C56

6 C57

6 C58

6 C59

6 C60

7 C61

7 C62

7 C63

8 C64

9 C65

10 C66

11 C67

12 C68

21 C69

22 C70

22 C71

23 C72

23 C73

23 C74

23 C75

23 C76

23 C77

23 C78

23 C79

23 C80

23 C81

23 C82

23 C83

23 C84

23 C85

23 C86

23 C87

23 C88

23 C89

23 C90

23 C91

23 C92

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23 C94

23 C95

23 C96

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23 C99

23 C100

23 C101

23 C102

23 C103

23 C104

23 C105

23 C106

23 C107

23 C108

23 C109

23 C110

23 C111

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23 C113

23 C114

23 C115

23 C116

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23 C119

24 C120

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24 C124

24 C125

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24 C134

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25 C136

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28 C148

28 C149

28 C150

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28 C158

28 C159

28 C160

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28 C163

28 C164

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28 C168

28 C169

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28 C172

28 C173

28 C174

28 C175

28 C176

28 C177

28 C178

28 C179

28 C180

28 C181

28 C182

28 C183

29 C184

29 C185

30 C186

30 C187

30 C188

30 C189

30 C190

30 C191

30 C192

30 C193

31 C194

31 C195

31 C196

31 C197

31 C198

31 C199

31 C200

31 C201

31 C202

32 C203

32 C204

32 C205

32 C206

32 C207

32 C208

32 C209

33 C210

34 C211

35 C212

2 C213

2 C214

2 C215

2 C216

2 C217

2 C218

2 C219

2 C220

2 C221

2 C222

2 C223

2 C224

2 C225

2 C226

2 C227

2 C228

2 C229

3 C230

3 C231

3 C232

3 C233

3 C234

3 C235

3 C236

3 C237

3 C238

3 C239

12 C240

12 C241

12 C242

12 C243

12 C244

12 C245

12 C246

12 C247

23 C248

23 C249

23 C250

23 C251

23 C252

23 C253

23 C254

23 C255

23 C256

23 C257

23 C258

23 C259

23 C260

23 C261

23 C262

23 C263

23 C264

23 C265

23 C266

23 C267

23 C268

23 C269

24 C270

24 C271

28 C272

28 C273

28 C274

28 C275

28 C276

28 C277

28 C278

28 C279

28 C280

28 C281

28 C282

28 C283

28 C284

28 C285

28 C286

28 C287

28 C288

28 C289

30 C290

30 C291

31 C292

31 C293

31 C294

31 C295

31 C296

32 C297

32 C298

32 C299

32 C300

32 C301

36 C302

37 C303

38 C304

39 C305

40 C306

41 C307

41 C308

41 C309

41 C310

41 C311

41 C312

42 C313

42 C314

42 C315

43 C316

43 C317

44 C318

45 C319

46 C320

47 C321

48 C322

49 C323

50 C324

51 C325

51 C326

51 C327

51 C328

51 C329

51 C330

51 C331

51 C332

52 C333

52 C334

52 C335

52 C336

52 C337

52 C338

52 C339

52 C340

53 C341

55 C342

55 C343

55 C344

55 C345

55 C346

55 C347

55 C348

78 C349

78 C350

81 C351

82 C352

83 C353

83 C354

83 C355

83 C356

83 C357

83 C358

83 C359

83 C360

84 C361

85 C362

86 C363

87 C364

88 C365

89 C366

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89 C372

89 C373

89 C374

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90 C385

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91 C396

91 C397

91 C398

91 C399

91 C400

91 C401

91 C402

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91 C404

91 C405

91 C406

91 C407

91 C408

91 C409

C410

91 C411

91 C412

92 C413

93 C414

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95 C416

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96 C418

96 C419

96 C420

96 C421

96 C422

96 C423

96 C424

96 C425

96 C426

96 C427

96 C428

96 C429

96 C430

96 C431

96 C432

96 C433

96 C434

96 C435

96 C436

96 C437

97 C438

97 C439

97 C440

97 C441

97 C442

97 C443

98 C444

98 C445

98 C446

98 C447

98 C448

98 C449

99 C450

99 C451

99 C452

99 C453

99 C454

99 C455

100 C456

100 C457

100 C458

100 C459

101 C460

101 C461

101 C462

101 C463

1 C464

4 C465

102 C466

103 C467

104 C468

105 C469

106 C470

107 C471

107 C472

107 *prepared according to example number

Lengthy table referenced here US11632957-20230425-T00001 Please refer tothe end of the specification for access instructions.

Lengthy table referenced here US11632957-20230425-T00002 Please refer tothe end of the specification for access instructions.

Lengthy table referenced here US11632957-20230425-T00003 Please refer tothe end of the specification for access instructions.

Lengthy table referenced here US11632957-20230425-T00004 Please refer tothe end of the specification for access instructions.

LENGTHY TABLES The patent contains a lengthy table section. A copy ofthe table is available in electronic form from the USPTO web site(https://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US11632957B2).An electronic copy of the table will also be available from the USPTOupon request and payment of the fee set forth in 37 CFR 1.19(b)(3).

The invention claimed is:
 1. A molecule having the following formula

wherein: (A) R¹ is selected from the group consisting of H, F, Cl, Br,I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl,(C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl,(C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl,(C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl,S(C₁-C₆)haloalkyl, S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl,(C₁-C₆)alkyl-S(O)₂NH₂, and (C₁-C₆)haloalkyl-S(O)₂NH₂; (B) R² is selectedfrom the group consisting of H, F, Cl, Br, I, CN, NH₂, NO₂,(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,(C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy,S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl,S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl, (C₁-C₆)alkyl-S(O)₂NH₂, and(C₁-C₆)haloalkyl-S(O)₂NH₂; (C) R³ is selected from the group consistingof H, F, Cl, Br, I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,(C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy,(C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl,(C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl,S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl,S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl, (C₁-C₆)alkyl-S(O)₂NH₂, and(C₁-C₆)haloalkyl-S(O)₂NH₂; (D) R⁴ is selected from the group consistingof H, F, Cl, Br, I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,(C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy,(C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl,(C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl,S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl,S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl, (C₁-C₆)alkyl-S(O)₂NH₂, and(C₁-C₆)haloalkyl-S(O)₂NH₂; (E) R⁵ is selected from the group consistingof H, F, Cl, Br, I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,(C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy,(C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl,(C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl,S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl,S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl, (C₁-C₆)alkyl-S(O)₂NH₂, and(C₁-C₆)haloalkyl-S(O)₂NH₂; (F) R⁶ is selected from the group consistingof H and (C₁-C₆)alkyl; (G) R⁷ is selected from the group consisting ofH, F, Cl, Br, and I; (H) R⁸ is selected from the group consisting of F,Cl, Br, and I; (I) R⁹ is selected from the group consisting of H and(C₁-C₆)alkyl; (J) Q¹ is selected from the group consisting of O and S;(K) Q² is selected from the group consisting of O and S; (L) R¹⁰ isselected from the group consisting of H, (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₁-C₆)haloalkyl, (C₁-C₆)alkyl(C₁-C₆)alkoxy, C(═O)(C₁-C₆)alkyl, and(C₁-C₆)alkoxyC(═O)(C₁-C₆)alkyl; (M) R¹¹ is selected from the groupconsisting of H, F, Cl, Br, I, CN, NH₂, NO₂, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl,(C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,(C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy,S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl,S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl, (C₁-C₆)alkyl-S(O)₂NH₂, and(C₁-C₆)haloalkyl-S(O)₂NH₂; (N) R¹² is selected from the group consistingof H, F, Cl, Br, I, CN, NH₂, NO₂, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,(C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy,(C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl, (C₂-C₆)haloalkenyl,(C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy, S(C₁-C₆)alkyl,S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl,S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl, (C₁-C₆)alkyl-S(O)₂NH₂, and(C₁-C₆)haloalkyl-S(O)₂NH₂; (O) X¹ is selected from the group consistingof (1) N, (2) NO, and (3) CR¹³, wherein R¹³ is selected from the groupconsisting of H, F, Cl, Br, I, CN, NH₂, NO₂, CHO, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl, (C₂-C₆)alkynyl,(C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,(C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy,S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl,S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl, (C₁-C₆)alkyl-S(O)₂NH₂,(C₁-C₆)haloalkyl-S(O)₂NH₂, and triazolyl; (P) X² is selected from thegroup consisting of (1) N, (2) NO, and (3) CR¹⁴, wherein R¹⁴ is selectedfrom the group consisting of H, F, Cl, Br, I, CN, NH₂, NO₂,(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl, (C₃-C₆)cycloalkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₃-C₆)halocycloalkyl,(C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkenyl, (C₁-C₆)haloalkoxy,S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, S(C₁-C₆)haloalkyl,S(O)(C₁-C₆)haloalkyl, S(O)₂(C₁-C₆)haloalkyl, (C₁-C₆)alkyl-S(O)₂NH₂, and(C₁-C₆)haloalkyl-S(O)₂NH₂; (Q) X³ is a substituted or unsubstitutedheterocyclyl, wherein said heterocyclyl is selected from the groupconsisting of indolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl,pyridyl, pyrimidinyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl,triazinyl, [1,2,4]triazolo[1,5-c]pyrimidinyl, triazolyl,2,3-dihydrophthalazine-1,4-dionyl, indolinyl, andpyrimidine-2,4(1H,3H)-dionyl, wherein substituents are selected from thegroup consisting of F, Cl, Br, I, H, CN, NH₂, NO₂, (C₁-C₆)alkoxy,(C₁-C₆)alkyl, (C₁-C₆)haloalkoxy, (C₁-C₆)haloalkyl, (C₂-C₆)haloalkenyl,(C₃-C₆)halocycloalkenyl, and (C₃-C₆)halocycloalkyl; wherein thecarboxamido, and the phenyl, which are bonded to the cyclopropane, arein the R,R configuration; and N-oxides, agriculturally acceptable acidaddition salts, solvates, isotopes, resolved stereoisomers, andtautomers, of the molecules of Formula One.